
By .Dr. H. Bourges, 



1111 



LIBRARY OF CONGRESS. 

KC \2>tt 
©|np 0qtijw$t $0 



UNITED STATES OF AMERICA. 



SPECIAL NOTE. 

It was originally designed to publish this book in the 
■series of 1S93, and the covers were so dated. But as the 
manuscript was not received early enough for publication in 
that series, the volume appears in the Leisure Library for 
1894: hence the discrepancy between the dates on cover 
and title page. 



A TREATISE 



ON 



DIPHTHERIA. 



i 



DR. H. BOURGES. 



Translated by E. P. Hurd, M.D., 

Member of the Massachusetts Medical Society; Medical Examiner for 

the Third Essex District, Massachusetts ; Member of the Climato- 

logical Society ; one of the Physicians to the Ne-wbury- 

port Hospital; Professor of Pathology in the 

College of Physicians and Surgeons, 

Boston, Massachusetts. 




mi - r,.^-i*h-r~ 



GEORGE S. DAVIS, 

DETROIT, MICH. 



IIP 




Copyrighted by 
GEORGE S. DAVIS. 



TABLE OF CONTENTS. 



Page 

Translator's Preface i-xxii 

Author's Preface i- 2 

Diphtheria — History 3- 10 

Etiology and Bacteriology n- 37 

The Diphtheria Poison 38- 48 

Secondary Infections in Diphtheria 49- 50 

The Pseudo-Diphtheritic Bacillus 51-55 

False Diphtherias 56- 57 

Animal Diphtheria 58-63 

Symptoms: Of Bacillary Infection; of Systemic 

Poisoning 64- 89 

Complications Due to Secondary Infections 90- 94 

Clinical Forms 95-103 

Diphtheria in Adults 104-105 

Secondary Diphtherias 106-107 

Progress. Duration, Termination 108-111 

Prognosis 112-114 

Diagnosis 115-119 

False Diphtherias 120-125 

Pathological Anatomy 126-131 

Lesions Produced by the Diphtheria Poison 132-143 

Lesions Due to Secondary Affections 144-145 

Treatment: Local; General; Treatment of Certain 
Signs of Intoxication; Treatment of Secondary 
Infections; Hygiene of Convalescence 149-167 



TRANSLATOR'S PREFACE. 



Probably no disease is the subject of more general 
interest to physicians than diphtheria, as none is a 
more favorite topic of discussion at medical meetings. 
Recent bacteriological researches have wonderfully- 
advanced our knowledge of its etiology, while the 
therapeutics of diphtheria have hardly kept pace with 
this progress. The remedies proposed are legion, but 
all too poorly fulfill their end, and the mortality from 
this disease still remains very high. We are still 
without a specific, though the profession is looking 
for one; but physicians are learning more intelligently 
to combat diphtheria, and the gains which prophylaxis 
has made are great. 

Under the head of the nature of diphtheria, there 
are two points to consider: first, the question of its 
microbial origin; second, whether it is primarily a 
local or a general disease. 

i. Till within a few years, nothing definite has 
been known about the contagion of diphtheria. There 
is now a growing disposition to accept as substantiated 
the claims alleged in behalf of the Klebs-Loeffier ba- 
cillus, especially in view of the recent confirmation of 
these claims by Roux and Yersin, of Paris, also by 
Drs. Abbot and Welch, of Baltimore. This bacillus 
is about as long and twice as thick as the tubercle 
bacillus; its extremities are rounded; it is immovable; 
it forms groups of chains, each element of which be- 
comes club-shaped at its extremity. It is found ex- 
clusively in cases of diphtheria, in or beneath the false 
membranes; has been in vain sought in the blood and 
viscera. Culture experiments, made first by Loeffler 
in 1884, subsequently by Roux and Yersin, appear to 



have been successful; and with the product of pure 
cultures, the disease in all its essential features— not 
even the secondary paralysis in the experiments of 
the French bacteriologists being lacking— has been 
reproduced in animals. These experiments have 
been in part confirmed by Kolisko and Paltauf, of 
Russia, and by Drs. Welch and Abbot, of the Johns 
Hopkins Hospital; the latter have noted the invari- 
able concomitance of the Klebs bacillus with the false 
membranes of true diphtheria. Other associated 
microbes, which doubtless have a role in the necrotic 
phenomena, have been observed in diphtheritic mem- 
branes, notably the Streptococcus diphtheria of Prudden, 
which seems to be identical with the Streptococcus 
erysipelatodes and the Streptococcus pyogenes. Prudden, 
in fact, assigns to this micro-organism the principal 
part in the production of false membranes. 

2. With regard to the second question, while 
there is not yet unanimity among the authorities, 
there seems to be preponderant evidence that diphtheria 
is primarily a local disease, the microbe first causing a 
local inflammation, necrosis, and fibrinous exudation, 
then elaborating in the false membranes a peculiar 
poison— a toxalbumen,— which is absorbed, infects 
and prostrates the organism. 

It is true that there are difficulties attending this 
view in its application to all clinical cases; the gravity 
of the phenomena of infection is not always in pro- 
portion to the extent of the false membranes, and 
with an inconsiderable amount of local lesion the pa- 
tient may from the first be overwhelmed by the toxic 
accidents. Cadet de Gassicourt makes much of this 
argument, and classes such cases under the head of 
"diphtheria of hypertoxic form." On the other hand, 
it is equally true that there are benign cases where, 



with well defined patches of false membrane covering 
considerable areas, the constitutional symptoms are 
trifling and almost nil. 

There seems to be no better way to arrive at a 
true conception of diphtheria than by pathological 
experimentation, the results of which always bear out 
the view above stated of a primarily local origin of 
the disease. This is not the place for a statement of 
facts such as Oertel has given in his article on 
" Diphtheria " in the first volume of Ziemssen's Cyclo- 
paedia, and which show conclusively that diphtheria, 
when induced in animals by the inoculation of bits of 
false membrane, is always at first local, fixing itself at 
the point of infection, and thence radiating inwardly. 
In harmony with this induction is the experience of 
Roux and Yersin with the soluble filtrates of diph- 
theritic cultures, which, injected in animals, produce 
septic accidents identical with the general constitu- 
tional effects of diphtheria in man. In accord with 
this doctrine, we may explain the grave hypertoxic 
cases as cases of unusual susceptibility to the disease, 
where the poison, though coming from only a small 
centre, is rapidly absorbed, and meets with but feeble 
resistance. In the benigti cases alluded to, though the 
diphtheritic focus was of considerable extent, either 
the conditions for the elaboration and absorption of 
the poison were unfavorable, or the vital forces of the 
organism were peculiarly resistant to its influence; 
we are not without analogies which will enable us to 
understand such cases in conformity with the view 
that diphtheria is primarily a local disease. 

The treatment of diphtheria will naturally vary 
somewhat in accordance with views held as to its be- 
ing primarily a local or a general disease. Those who 
believe in a primarily local origin will naturally have 



a strong interest in destroying in situ the morbid 
germs before they have had time to generate their 
virus and poison the organism. Under the other 
theory, the indications to promote local antisepsis and 
limit the spread of false membranes is equally recog- 
nized; but he who regards the diphtheritic plaques as 
only the expression of a general disease, bearing the 
relationship to the latter which the scarlatinal angina 
bears to scarlet fever, will not so strongly insist on 
energetic local treatment as he who looks upon the 
local lesion as the centre of the infection. Those, 
doubtless, that hold to the latter view have the most 
sanguine expectation that a specific will yet be dis- 
covered which, applied in time to the morbid focus, 
will nip the disease in the bud. 

Certainly the results of the cauterization treat- 
ment, carried out with the intent of destroying the 
microbe /'// situ, have not been remarkably successful, 
unless we except the apparently favorable experience 
with carbolic acid and with phenicated camphor of 
Archambault and Gaucher, at the Hopital des En- 
fants Malades; of Soulez, of Romorantin; of Sevestre, 
at Hopital Trousseau; and of Dubousquet-Laborderie 
{vide Bulletins et Memoires de la Socie'te de Me'decine 
Pratique, January 15, 1889). The method of these 
writers has been so highly vaunted that it deserves 
mention. The phenicated camphor is made of follows 
(formula given by Sevestre):* 

5 Camphor, 20 parts. 
Castor oil, 15 parts. 
Alcohol, 10 parts. 
Crystallized phenic acid, 5 parts. 
Tartaric acid, 1 part. 

Dissolve the phenic acid in the alcohol, add the camphor, 
then the tartaric acid, and finally the oil. 



* Sevestre: " Etudes de Clinique Infantile," 1S90, p. 210. 



Gaucher applies this preparation in the following 
way: 

" The mouth being widely opened and the tongue 
depressed, the operator will carry the swab charged 
with the liquid into the back part of the throat, apply- 
ing it to the tonsils or other parts that are covered 
with false membrane. He will rub vigorously the 
diseased surface, in order to detach and remove the 
diphtheritic membrane, which will come away in 
debris or flakes. After each rubbing, the swab should 
be washed in a carbolic solution. These frictions 
should be repeated several times at each seance till 
all the white patches have been removed or destroyed. 
A final application with the swab dipped in the 
caustic will be made to the throat, in order to touch 
all the surfaces which have been denuded and de- 
spoiled."! 

This operation is repeated morning and evening 
and in the interval of the cauterizations; large irriga- 
tion-injections are made every two hours into the 
throat, by means of a fountain syringe, of a 1:100 
carbolic solution. The pain of the cauterizations is 
sometimes very great, but may be mitigated by pre- 
viously spraying the throat with a cocaine solution. 

Despite the fact that signal and unparalleled suc- 
cess is claimed for this treatment (see statistics of 
Gaucher, Le Gendre, Dubousquet), it will not be 
likely to come into favor, on account of the painful- 
ness of the cauterizations, the swelling which follows 
them (which necessarily hinders deglutition), and the 
difficulty, if not impossibility, of application in young 
children. Theoretically, this method is excellent; 
practically it demands for its execution a pitiless 

f Bull, et M<?rn. de la Soc. de Mdd. Pratique, January 15, 
18S9. 



hardihood which few physicians possess. It is doubt- 
ful if in private practice the results would ever be 
even approximately as good as the French writers 
claim. The method of cauterizations is an old 
method, dating back to the times of Bonsergent, who 
cauterized the throats of young children with a red- 
hot iron, and Bretonneau, who did not even originate 
but who borrowed from physicians of a past age a 
practice which consisted in swabbing out the diph- 
theritic throat three or four times a day with fuming 
hydrochloric acid. Trousseau, Rilliet and Barthez, 
and others adopted substantially this procedure, 
using muriatic acid, saturated solutions of nitrate of 
silver, sulphate of copper, etc., forcibly removing 
false membranes where they could, and cauterizing 
the denuded surfaces. 

It is needless to say that the method of cauteriza- 
tions, as formerly advocated by this school, has been 
deservedly pronounced a failure, and is now a thing 
of the past. Cauterization, as Cadet de Gassicourt 
says, does not prevent the patches from forming 
anew; it causes pain and dysphagia, and the more 
the derm is denuded the more the extension of false 
membranes is increased and promoted. 

It may, however, be said, in defense of the later 
method proposed by Gaucher and his colleagues, 
that it is less severe than the methods of Bretonneau 
and his school, as phenic acid is comparatively a mild 
caustic, and, in the diluted form in which it is med, 
effects little destruction of tissue, while being nocuous- 
or destructive to the microbes. It may well be, as 
these writers claim, that, in cases of adults where this 
heroic treatment can be properly carried out, it may 
save life where other methods fail, due pains being 
taken to keep the throat well disinfecied in the inter- 



vals of cauterizations by means of antiseptic sprays 
and irrigations. Most authorities condemn all inter- 
ference with the false membranes till they are sepa- 
rated from their attachments, and can be removed 
without violence to the parts beneath them. 



II. 

At the meeting of the Soci^te de Medecine 
Pratique, January 3, 1889, when the paper of Dubous- 
quet was read, commending the method of cauteriza- 
tions advocated by Gaucher, Guelpa (who made 
considerable stir in the Society discussions of diph- 
theria) demanded if the good results which had been 
claimed for this method might not have been due 
largely, if not altogether, to the frequent irrigations 
which formed a part of the treatment. The majority 
present at this and subsequent meetings were under- 
stood to deprecate all use of strong caustics, as well 
as the forcible removal of the false membranes. 

At another meeting, held April 4th, and at a 
subsequent meeting of the Therapeutical Society, 
Guelpa read a long paper in answer to the question, 
" Why, in the treatment of diphtheria, do the same medi- 
caments give satisfactory results to some practitioners and 
negative results to others ? " 

He criticised the numerous remedies which have 
been advised in this disease. Some, as resorcin, have 
been extolled as almost specific. This medicament, 
so successful in the hands of Callias, saving nearly 
all his patients, has not proved efficacious in the prac- 
tice of Cadet de Gassicourt, who has used it in all 
degrees of saturation. 

Phenic acid has been highly commended by 



excellent authorities, notably Kempster, Jacobi, 
Oertel, Billington, Smith, and Mackenzie, but others 
have not found its effects especially favorable. The 
same judgment may be passed upon caustic soda and 
glycerin, lime-water, lemon-juice, boric acid, tannin, 
iodoform, and even perchloride of iron. 

While recognizing the fact that there is a differ- 
ence in the malignancy of epidemics, and that reme- 
dies act differently at different periods of the same 
epidemic, the writer, nevertheless, felt compelled to 
conclude that the same medicament in the hands of 
certain practitioners had given favorable results, 
while it had failed completely with others. The 
cause, he believed, he had found. We quote his 
words: 

" M. Callias, repeating the trials with resorcin 
made by Andeer, Leblond, and Joja, is careful to tell 
us that he mops out the throat every hour, night and 
day, with a 5-per-cent. solution. To this he adds 
spraying the buccal and nasal cavities with a 2 per- 
cent, solution every two or three hours, and fumiga- 
tions, twice or three times a day, with resorcin in 

substance, sublimated by a moderate heat 

Note the fact that the throat is swabbed out every 

hour tiight and day With regard to phenic 

acid, M. Roulin tells us that he employs his carbolic 
irrigations every hour in the twenty-four, and claims 
extraordinary success. Kempster and Rothe paint 
the throat every hour with a strong carbolic mixture, 
and use every half-hour a weaker preparation for a 
gargle. Giovanni Calligari applies every quarter of 
an hour to the diseased places a i-per-cent. carbolic 
solution. Jacobi sprays and irrigates very frequently 
with carbolic solutions. Oertel declares that phenic 
acid constitutes the best and surest means at our dis- 



posal for combating diphtheria. But this medica- 
ment should be employed with energy. The practi- 
tioner should spray every two hours, every hour, or 
oftener, according to the age of the patient, with a 5- 
per-cent. solution. The atomizing tube should be 
made to enter the patient's mouth. All practitioners 
have obtained excellent results from this frequent 
use of the carbolic preparations. Oertel, in fifty-one 
cases, did not lose a patient. 

"If we come to the employment of perchloride 
of iron in diphtheria, we have still less difficulty in 
establishing the fact that the disease is the more 
surely and rapidly overcome the more frequently and 
thoroughly the part which is the seat of the disease 
is medicated with the solution employed. Thus, we 
see the Aubruns, father and son, administer to their 
diphtheritic patients a spoonful of a 4-per-cent. solu- 
tion every five minutes during the day, and every 
quarter of an hour at night. Jacobi advises to give 
the solution of perchloride ot iron every quarter of an 
hour, or every hour, according to the gravity of the 
disease. Colson, Clar, Noury also administered this 
medicament about every half- hour, day and nighty 

It will be seen from the above extract that, in 
the estimation of the writer, it is the frequency and 
thoroughness with which the applications are made that 
are the principal elements of success. Firmly believ- 
ing in the local origin of diphtheria, and that if the 
seat of the disease can be kept antiseptically clean 
the microbes will be impeded or thwarted in their de- 
velopment, and blood-poisoning and further extension 
by contiguity of the disease prevented, he advocates 
irrigations every hour of the nasal cavities (in the 
event of nasal diphtheria existing) and of the throat 
with a 5-per-cent. chloride-of-iron solution. For this 



purpose, a common hand rubber-ball syringe will 
answer the purpose; the capacity of the rubber ball 
should be about four ounces. The nozzle, which 
should be of hard rubber, is inserted successively into 
each nostril, and the solution injected with sufficient 
force to penetrate the pharynx. When the irrigation 
is to be made by mouth, the nozzle can be inserted 
behind the last molar tooth. Generally there is no 
great difficulty. The child is held in the lap of the 
nurse or medical attendant, with the head pressed 
against the chest of the latter; and the cannula of the 
syringe is slipped in behind the last molar. Generally 
at this moment the mouth is opened wide in the strug- 
gle, and it is very easy to inject with full stream quite 
a quantity of the liquid. Part of the liquid is swal- 
lowed, but the most of it flows back. For the nasal 
douches a weaker solution is recommended (3 per 
1000). 

Guelpa regards these irrigations as of great use 
" in fortifying the surrounding mucous membrane and 
in wa-hing away the septic products, whose absorp- 
tion constitutes the true danger of the disease, and 
whose accumulation serves to irritate the contiguous 
mucosa and render it a fit soil for the development of 
the diphtheritic bacillus." As for parasiticides, there 
are probably at least a dozen agents, any one of 
which, if used with sufficient frequency, will almost 
equally well fulfill the leading indication; phenic acid 
and perchloride of iron are among the safest; resorcin 
demands further trials; corrosive sublimate (1 to 5000) 
would probably be the best if the free use of this 
bactericide were not attended with some danger. The 
intent of the irrigations is not to clear the throat or 
other diseased surface of false membranes; the false 
membrane, says Guelpa, need give no trouble as long 



as it remains within certain fixed limits. The true 
end of treatment is to prevent the pseudo-membrane 
spreading over too large a surface. If the false mem- 
brane is not allowed to extend, if the subjacent tissues 
are not irritated by the treatment, the diphtheritic 
patches will become loosened, and fall off in the 
course of a week; if other patches form in their 
places, these are always more limited, are thinner, 
and sooner mature and fall off. 

Cousot, of Brussels, in the Journal de Me'decifie 
et de Chirurgie Pratique, April, 1889, also insists that 
the treatment of diphtheria at its commencement 
should be chiefly local; that it should destroy the 
germs of diphtheria wherever they appear; should 
entirely prevent putrefaction, and, at a later stage, 
when systemic infection occurs, local remedies should 
still be vigorously applied, and additional measures 
employed to relieve the general symptoms. The 
medicine for local use which Cousot believes best 
fulfills these indications is a mixture of acacia, spirits 
of peppermint, and tannin, employed in the following 
formula: 

Mucilage of acacia, 100 parts. 

Tannin, 10 parts. 

Spirits of peppermint, 2 to 20 parts. 

The syringe is employed for its application, for 
this alone permits sufficient irrigation and impregna- 
tion of the inflamed surfaces. If the false membrane 
occupies the pharynx, tonsils, or nasal fossae, what- 
ever may be the degree of its development, it is 
necessary to inject the mucilage and tannin into the 
mouth and nares every tivo hours. Whatever may be 
the degree of decomposition of the diphtheritic patch, 
its putrid odor ceases on the first application, and it 
contracts and becomes detached. The efficacy of 



this method seems to be established by abundant 
statistics.* 

Whatever may be said of the efhcacy of irriga- 
tions, they are not always easily administered, and 
the pursuance of this treatment every hour or two 
day and night is certainly fatiguing to the patient, 
and must more or less interfere with sleep. To be 
sure, according to the French authorities most zealous 
in advocating these injections, in a disease fraught 
with so much danger as diphtheria, that treatment 
which will save the most lives should be adopted, no 
matter how difficult of execution. The question, then, 
for solution is this: Is the method of frequent irriga- 
tion the best method of meeting the indication ? 
Good authorities have claimed most excellent results 
from milder measures. Thus a child may be made to 
frequently swallow a solution of chloride of iron with- 
out great difficulty, and this would appear to accom- 
plish the same end as the forcible injection of the 
same fluid. Sprays containing carbolic acid can be 
used alternately with the mixture, and port wine 
(which contains tannin and alcohol) can be adminis- 
tered freely in the interval. An occasional irrigation, 
or even mopping out the throat, may be practiced, the 
swabbing being done with due gentleness, so as not 
to cause lesions or excoriations, to be new centres of 
infection. 

These are the principles of treatment advocated 
by numerous American authorities, as J. Lewis Smith, 
Abram Jacobi, C. E. Billington. Smith and Billing- 
ton make much account of the frequent administration 
of tincture of chloride of iron. The following is a 
favorite prescription of the latter: 



* Cited from Sajous's "Annual." 



B Tinct. ferri chloridi, 3 iss. 
Glycerin, ) f - . 
Water, f aat 3J- 

M. Sig. : A teaspoonful every hour. 

Smith gives about the same quantity of iron 
hourly, combined with four grains of potassium chlor- 
ate; the vehicle is simple syrup. Both deprecate 
forcible removal of the pseudo-membranes and all 
energetic topical applications by sponge or probang. 
Besides the hourly dose of chloride of iron, Billington 
gives every hour a teaspoonful of a mixture of lime- 
water and glycerin, in which a little chlorate of potas- 
sium is dissolved. Both make much account of spray- 
ing with the hand atomizer, and prescribe solutions of 
carbolic acid and lime-water for that purpose. A 
favorite combination of Billington's is the following: 

~R, Acid, carbolic, TT[xv. 
Aquae calcis, f § vj. 

M. Sig: To be applied to the throat very frequently in 
the form of spray. 

In nasal diphtheria, the nares should be syringed 
out two or three times a day with salt and water, then 
with a mixture of salicylic acid, ten grains, with thirty 
of sulphate of sodium, to glycerin half a fluidounce, 
and water two and a half fluidounces. For this in- 
jection, a hard rubber ear-syringe may be employed. 

In adult patients, with particularly unyielding 
diphtheritic patches, once or twice a day a mixture of 
tincture of chloride of iron two parts, glycerin one part, 
may be carefully applied to the surface of the mem- 
brane with the tip of a camel-hair pencil. It seems, 
says Billington, to shrivel up the membrane and has- 
ten its disintegration. But strong applications should 



never be "mopped" over the inflamed throat, and it 
is not thought safe, as a rule, ever to apply a brush to 
a child's throat. 

III. 

Fresh evidence has been steadily accumulating 
to prove the invariable causal connection between 
Loeffler's bacillus and ordinary diphtheria, and Prud- 
den has recently made an important communication 
in which he concedes to this microbe the primary role 
in the etiology of this disease {Medical Record, No. 
1067). Dr. Welch, of the Johns Hopkins University, 
has published the results of his and Dr. Abbot's studies 
at the Johns Hopkins Hospital, and these add striking 
confirmation to the data on which has been founded 
the doctrine of the primarily local origin and develop- 
ment of the infection — a doctrine which, we observe, 
has been lately conceded by Cadet de Gassicourt, 
though opposed in the first edition of his masterly 
work, " Lecons Cliniques sur les Maladies des En- 
fants" (t. iii, 1884). 

"Of capital importance," says Professor Welch, 
"is the establishment of the fact that the diphtheritic 
bacillus develops only locally at the site of infection, 
and does not invade the tissues or the circulation. It 
is found only in the diphtheritic pseudo-membrane, 
and not even in the subjacent mucous membrane. 
Indeed, it is only the superficial parts of the false 
membranes which contain the bacilli. The deter- 
mination of this fact gives at once a clear and de- 
cisive answer to the long-mooted question as to the 
primarily local or constitutional nature of diphtheria. 
The germ which causes this disease not only makes 
its first appearance and multiplies where the pseudo- 



membrane is formed, but it does not even subsequently 
invade the blood and organs. As we shall see later, 
the constitutional symptoms are due to the reception 
of a chemical substance or substances of remarkable 
toxic properties produced by the local development 
of the diphtheritic bacillus."* 

We are, then, again brought around to the 
primary indication of treatment, made more and more 
certain and imperative as researches accumulate: to 
destroy the contagium in situ before the microbes have 
had time to elaborate their poisons and infect the organism. 

It would seem that diphtheria primarily occurring 
on any accessible cutaneous surface might always be 
readily arrested by deep, thorough cauterization. 
Such cases are, however, very rare, and, when they 
occur, generally follow inoculation of a wound. The 
primary lesion is too often on mucous surfaces, which, 
like the posterior nares and the larynx, are not easily 
amenable to thorough topical treatment. 

What shall be the treatment of the toxaemia re- 
sulting from absorption of the poisonous principles 
produced by the bacilli ? Every physician is familiar 
with the change which often takes place at a variable 
time — two, three, or four days — after the first appear- 
ance of the patches; the sthenic symptoms, on which 
hope was based, give way to symptoms of prostration, 
and the system seems overwhelmed by a paralyzing 
poison. 

Ignorant of the proper antidotes of this poison, 
if such exist, we can only combat it on general prin- 
ciples, by stimulants and tonics. The internal em- 
ployment of corrosive sublimate in frequent doses of 
jfar to \ g ra ^ n » or °f calomel (^ to i grain every hour), 
is no longer justified on the ground of a microbicidal 

* 'Medical Xctvs, May 16, 1S91, p. 559. 



action exercised by these drugs, for the constitutional 
symptoms are not due to microbes, but to their soluble 
products, and there is no evidence that mercurials 
destroy these products in the blood. 

The same judgment must be passed upon the 
sulphites and hyposulphites, counseled by Giacchi 
and Polli, in Italy, phenic and salicylic acids, vaunted 
by Besnier in France and Foutheim in Germany, and 
benzoate of sodium, recommended by Helferich, 
Sanne, Love, and others. 

If the internal use of corrosive sublimate has 
been attended with good results, these might very 
properly be attributed to the topical action of the 
mercurial while passing over the mucous membranes 
in the act of deglutition, and not to any effect on the 
blood. Per contra, there is reason to believe that the 
tinctura ferri chloridi, one of the best topical rem- 
edies, may exercise beneficial constitutional effects. 
Recent investigations (as those of Ferguson) have 
shown that the diphtheritic poison rapidly spoils the 
blood-corpuscles; there are still lacking observations 
which directly show that tincture of iron retards this 
disintegration, although good authorities, basing them- 
selves on large clinical experience, believe that this 
preparation, freely and continually administered, does 
have this power. Dr. Whittier believes that this 
medicine, given so as to saturate the system, is the 
best that can be employed. Baruch prescribes hourly 
doses, in quantity varying from eight to twenty-five 
drops, mixed with glycerin and water. Food and 
stimulants are administered before the iron, but not 
immediately afterwards, so that the iron may first 
have a local effect on the fauces. 

" That now, after thirty years' constant use of 
the tincture of chloride of iron in both hemispheres, 



there is an almost unanimous verdict in its favor, ren- 
ders it probable that the few who have not observed 
good effects have treated unusually bad cases, or have 
given the medicine in small and inadequate doses." 
(Dr. J. Lewis Smith.) 

The employment of pilocarpine (either by potion 
or by subcutaneous injection), first recommended by 
Guttman, has gone out of use. Archambault, Schmidt, 
Alfoldi, Jacobi, and J. Lewis Smith have pointed out 
the dangers of this treatment. Sudden filling up of 
the bronchial tubes with secretion, and heart-failure, 
have not unfrequently followed its use. 

Quinine has been much prescribed in diphtheria, 
and when given in sufficient doses doubtless does 
have some tonic effect; it is, however, depressing in 
large doses, and, on account of its bitterness, is always 
repugnant to children. " It does not," says Smith, 
"seem to exert any decided action upon the local 
affections or blood-poisoning in diphtheria." 

The same judgment may be passed on the inter- 
nal administration of chlorate of potassium, a remedy, 
doubtless, too much administered, being of no specific 
value, and being toxic in large doses. 

Alcoholic stimulants have an important place in 
the therapy of diphtheria, and many authorities, as 
Jacobi, recommend quantities that in health would 
be toxic. J. Lewis Smith does not hesitate to give a 
teaspoonful of good brandy or whiskey hourly to a 
child of five years, and Jacobi states that he has often 
seen children get well with ten ounces a day who were 
doing badly with three or four. Cadet de Gassicourt 
(" Traite" Clinique," etc., t. iii) would give to a young 
infant from half an ounce to two ounces of old rum 
or brandy per day. 

Caffeine, camphor, strychnine, and Siberian musk 



have been recommended to counteract depression and 
heart-failure. Jacobi believes musk to be the best 
stimulant in urgent cases of heart-failure. '• If," he 
says, " ten to fifteen grains, given [in thin mucilage] 
within three or four hours to a child of one or two 
years, do not restore a healthy heart action, the prog- 
nosis is bad." 

Zannelis {Bull, et M/m. de la Soc. de Me'd. Pra- 
tique, 1889) speaks favorably of strong infusions of 
tea or coffee in adynamic stages. Nourishment should 
be for the most part liquid, for obvious reasons; the 
digestive functions are depressed, and the frequent 
ingestion of medicine and alcoholic stimulants more 
or less interferes with the secretion of gastric juice 
and the formation of peptones; the mechanical ob- 
stacles to deglutition are frequently considerable, and 
anorexia is generally a marked symptom in the toxic 
stage. Hence milk, beef-juice, liquid peptones, raw 
eggs beaten up in milk, given in such quantities as 
can be tolerated and not too often to interfere with 
the administration of antiseptic medicines and of 
alcoholic stimulants, are especially ind cated. 

In concluding this rather long therapeutic re'sumi, 
I would repeat that physicians are likely to profit 
more and more from the exact knowledge which we 
are acquiring of the nature of diphtheria. h\\ pathies 
must sink into insignificance before scientific medi- 
cine, and the Bacterial Pathology is giving us a scien- 
tific basis for therapeutics. 

The importance of the new etiology has justified 
a restatement of the whole subject, and therefore the 
present treatise by a well known French pathologist 
and master of bacteriology will be welcome in an 
American dress. 

E. P. HURD, M.D. 

Newburyport, Mass., Jan. 1st. 1894. 



AUTHOR'S PREFACE. 



Diphtheria is a contagious disease due to the bacillus 
discovered by Klebs and studied by Loeffler. The point of 
infection chosen by this bacillus is almost always a mucous 
surface, the pharynx or the air-passages preferably (some- 
times an excoriated region of the cutaneous surface); here 
it forms colonies and pullulates, determining the development 
of a fibrinous pseudo-membrane, of which it occupies the 
superficial stratum. There the microbe remains entrenched, 
never invading the organism nor entering the circulation. It 
may, in the same subject, be transplanted to many different 
points of the mucous or cutaneous surface, but causes only 
foci of local infection. But though the organism does not 
become infected in its entirety, it may be poisoned, for the 
bacillus produces a very active toxine, demonstrated by 
Roux and Yersin, which is readily diffusible and penetrates 
the circulation. 

This disease comprehends two orders of symptoms: the 
one (localized at the point of infection, and harmful only by 
the mechanical accidents which it may provoke, such as the 
obstruction of the air-passages by the false membrane) due 
to the bacillus; the other, marking a profound poisoning of 
the organism by the diphtheritic toxine, manifests itself by 
grave general troubles and profound lesions of the viscera. 
Diphtheria, then, is the resultant of these two agents, the 
bacillus and the poison. 

We are thus led in the description of the disease to 
class under two distinct heads the symptoms and lesions, 
according as they are due to the bacillus or to the diphthe- 
ritic poison. Often, too, in the course of diphtheria, a new 
microbic infection grafts itself upon the first; hence a third 
division, that of Secondary Infections. 



Such is the plan of our study of diphtheria. To the 
objection that the lesions and symptoms of the diphtheritic 
poison and of the secondary infections, respectively, have not 
yet been sufficiently studied or differentiated to insure accu- 
racy in classification, it may be answered that further 
researches will bring about the necessary rectifications^, 
meantime the general plan which I have adopted seems to 
agree best with what is now known of the disease. 

I have given very extensive proportions to the chapter 
on Bacteriology, and endeavored to furnish a description 
sufficiently minute and practical to enable those who have 
only elementary notions of bacteriological technics to re- 
peat the principal experiments. Moreover, the cultivation 
of the diphtheritic bacillus will ultimately constitute a capi- 
tal and indispensable element in the diagnosis of the disease, 
I have devoted a special paragraph to the false diphtherias, 
although the study of these, only recently undertaken, is far 
from being complete; this inchoate and undeveloped condi- 
tion stimulates to further tentatives in this direction. 

Lastly, I have not filled my book with the innumerable 
variety of therapeutic methods and agents which have been 
proposed for diphtheria; their very abundance gives the 
measure of their value. 



A TREATISE ON DIPHTHERIA. 



HISTORY. 

Several names deserve to be inscribed at the 
head of the history of diphtheria: that of Breton- 
neau, who made of this disease a morbid entity and 
gave it its name; that of Klebs, of Loeffier, who dis- 
covered the bacillus of diphtheria and determined its 
specificity; those of Roux and Yersin, who separated 
the poison of the bacillus and demonstrated its action. 

The history of diphtheria really commences with 
Bretonneau. It is true that divers manifestations of 
the disease had been recognized and often well de- 
scribed from the most remote antiquity. Such was 
the case with the Syriac or Egyptian ulcer observed 
by Aretaeus, of Cappadocia, and after him by Galen 
and Ccelius Aurelianus. We must then come down 
to the sixteenth century to find descriptions referable 
to diphtheria. An account of an epidemic of angina 
in Holland was written by Pierre Forest in 1557, and 
mention of pestilential anginas observed in Germany 
in 1565 is made by Jean Wierus. From this time 
onward, the disease is more frequently described, in 



the seventeenth century under divers names; garotillo 
in Spain, angina ulcerosa in Portugal, morbus slrangu- 
latorius in Italy. Next come the epidemics, better 
studied, of the first half of the eighteenth ecntury: 
that of Paris (gangrenous sore throat of Malonin and 
Chomel the elder); those of England, described by 
Fothergill, Starr, and Huxham; those of Sweden and 
of Germany. 

But up to this time the manifestations of diph- 
theria were regarded as expressions of gangrene: the 
false membrane was an eschar, and each localization 
of the disease was considered as a distinct affection. 

Home, in 1765, studied especially the laryngeal 
manifestations of diphtheria, and described them as a 
new disease under the name of croup. He was the 
first to recognize that the false membrane is not the 
product of gangrene, but of a superficial exudation. 
But he did not see the link which unites croup to ma- 
lignant angina, and he regarded them as two distinct 
diseases. In 1771, Samuel Bard essayed to demon- 
strate that simple angina, angina with extension to 
the larynx, and laryngitis when occurring alone, are 
but forms of the same disease. He considered the 
false membrane, not as an eschar, but as formed of 
concrete mucus. He could not, however, modify the 
opinion generally entertained, and the profession still 
continued to regard croup as a special disease. 

The question of croup being under discussion, 
and a prize having been offered by Napoleon I., in 



1807, for the best treatise 'on the subject; in one of 
the five memoirs that were regarded as especially 
meritorious — that of Jurine, of Geneva — we find em- 
phasized the reservations already formulated by Bard 
and Home respecting the gangrenous origin of malig- 
nant angina; and, moreover, Jurine affirms that croup 
is a frequent consequence of this kind of angina in 
children. These notions, however, remained undevel- 
oped until Bretonneau published the results of his 
labors (1818-1826). He showed that the false mem- 
brane of the larynx and trachea is continuous with 
that of the throat and nasal fossae, hence there is iden- 
tity of nature between the different localizations of 
one and the same disease, to which he gave the 
name of diphtheritis (from diphthera, a membrane). 
He endeavored to prove that the false membrane is 
but a fibrinous exudation covering the intact mucosa, 
and he maintained, even, that the ulcerous and gan- 
grenous processes cannot- be coincident with diph- 
theria. In his estimation, the disease is characterized 
by a specific local inflammation. 

Trousseau continued the researches of his mas- 
ter, but modified the conception of Bretonneau on the 
nature of the affection. He made of it a general in- 
fectious disease presenting the property of determin- 
ing upon different points of the economy a pseudo- 
membranous inflammation. He considered the false 
membrane not as an initial phenomenon, but as a con- 
sequence of the infection, and proposed to replace 



— 6 — 
the word diphtheritis, which gives too much promi- 
nence to the factor of inflammation, by the name 
diphtheria, which better designates a general disease. 
These notions, now recognized as inexact, since the 
bacteriological labors of Klebs and of Loeffler have 
been confirmed, nevertheless led Trousseau to the 
correct conclusion that death from diphtheria may be 
independent of the asphyxia, and the consequence 
simply of the systemic poisoning. Trousseau's error 
in regarding diphtheria as a general infectious disease 
was repeated by almost all pathologists up to the last 
few years. 

Despite Bretonneau's brilliant discoveries, the 
German school, under the leadership of Virchow, 
entrenched itself behind the anatomico-pathological 
findings, and again separated diphtheritic angina 
from croup. The microscope shows that below the 
false membrane in the pharynx the inflammation pen- 
etrates profoundly the chorion— is interstitial, in fact 
— while it remains quite superficial in the larynx and 
trachea. The German school admitted, then, two 
distinct diseases: one an infectious angina easily be- 
coming gangrenous; the other, exudative and purely in- 
flammatory—croup. Virchow and his pupils went still 
farther: the words diphtheria and croup served to des- 
ignate lesions of quite different origin. Every inter- 
stitial inflammation of the tissues became in their 
eyes diphtheritic, every superficial fibrinous exuda- 
tion croupous. Thus it came about that ulcero-mem- 



branous stomatitis was ranked among the diphtheritic 
inflammations; and there was a croupous nephritis, 
and a croupous pneumonia. These notions, which 
soon began to lose the support of clinicians, were 
destined to be abandoned when bacteriology demon- 
strated their falseness. 

After Bretonneau and Trousseau, the clinical 
features of diphtheria became well defined, and the 
pathological anatomy of the lesions was developed 
and elucidated by Virchow, Cornil, and others. At 
the same time the microscopy of the lesions was not 
advanced, and the intimate nature of the disease was 
unknown down to the time of the rise of microbiology 
and the development of modern views of infection. 
Some incomplete researches had been made in this 
direction when, in 1S83, at the Congress of Wies- 
baden, Klebs declared that he had stained a bacillus 
found in the false membranes of diphtheritic patients, 
which he considered as the specific agent of the dis- 
ease. According to his investigations, the bacilli of 
diphtheria scarcely attain the dimensions of those of 
tuberculosis; they begin by grouping themselves in 
the epithelium of the mucosa, whereupon an enormous 
dilatation of the vessels below the epithelium occurs, 
with blood stasis. Then follows the exudation of 
fibrin which raises the epithelium filled with bacilli. 
Klebs declares he has not been able to note the pres- 
ence of these micro-organisms in the viscera, although 
there were lesions in the lungs, the kidneys, the myo- 



cardium, and the peripheral nerves; gentian violet 
and methylene blue, which stain the parasites in the 
false membrane, do not show their presence in sec- 
tions of the viscera. He put forth the hypothesis 
that the lesions of the viscera may be produced by an 
irritant chemical substance furnished by the bacilli 
which pullulate on the surface of the diseased 
mucosa. 

The year following, Loeffler published in a long 
memoir the results of his brilliant labors on the bacil- 
lus of Klebs. He was the first to isolate and culti- 
vate it. Blood-serum is, he says, a good culture- 
medium. In a series of twenty-five cases of diphtheria, 
he almost always noted the bacillus in the false mem- 
brane, but never in the organs. With pure cultures 
he was able to provoke the formation, on excoriated 
mucous surfaces, of false membranes identical with 
those of diphtheria in the pigeon, the hen, the hare, 
and the guinea-pig. He has studied the effects of 
subcutaneous or intra-venous inoculation of the bacil- 
lus in a great number of animal species. Certain 
reasons leave him hesitating as to the specificity of 
this microbe. In several cases of typical diphtheria 
he was not able to discover it, and the animals in- 
oculated never presented true paralysis. Lastly, in 
one case he found a bacillus identical with that of 
Klebs in the saliva of a healthy child. 

In 1887, in a second memoir, Loeffler announced 
that in ten new examinations of diphtheritic mem- 



— 9 — 
branes he had found Klebs's bacillus in all. He also 
noted in the false membranes the pseudo-diphtheritic 
bacillus, much resembling the first, but without viru- 
lence when inoculated in animals. 

The preceding year, 1886, D. Espine reported to 
the Swiss-Romande Medical Society that he had 
noted the presence of the bacillus in preparations 
made with false membranes, and its absence from the 
non-diphtheritic anginas with white exudations. In 
1887 he confirmed his first discoveries. 

At the end of the year 1888, Roux and Yersin 
began the publication of a series of memoirs on the 
diphtheritic bacillus. They established the existence 
in animals of experimental paralyses consecutive to 
the inoculation of Loeffler's bacillus, and thus over- 
threw a strong argument of the opponents of the 
specificity of this bacillus. They also confirmed the 
constant presence of this agent in the false-diph- 
theritic membranes, studied its resistance, the attenu- 
ation and the reawakening of its virulence, and made 
new researches on the pseudo-diphtheritic bacillus of 
Loeffler and Hoffman, which they identified with the 
specific bacillus of diphtheria. 

But the most brilliant result of their labors was 

to show that the bacillus of Loeffler produces a poison 

of extreme activity — that the culture-broths, freed from 

microbes by filtration through porcelain, and then 

inoculated in animals, determine symptoms and lesions 

identical with those produced by injections of the 

cultures of the bacillus itself. 
3 vvv 



Since then, recent researches have shown that 
by the side of the pseudo-membranous products due 
to Loeffler's bacillus, there exist false diphtherias pro- 
voked by different microbes. 

During the last few years, attempts at vaccina- 
tion of diphtheria in animals have been made by 
Fraenkel and by Brieger and Behring. The results 
obtained by the latter seem very encouraging. 

Before concluding this chapter I may refer to the 
researches on the diphtheritic bacillus by Darier, 
Babes, Soerenson, Kolesko, Paltauf, Zarnicko, Ort- 
mann, Spronck of Utrecht, Escherich, and Klein; on 
the diphtheritic poison, by Brieger and Fraenkel, 
Wassermann and Proskauer, and Gamaleia; on the 
secondary infections in diphtheria, by Darier, Prudden 
and Northrup, Mosny, Morel, and Netter. 



ETIOLOGY AND BACTERIOLOGY. 

General Etiology. — It is to-day undisputed 
that the efficient cause of diphtheria is the Klebs, 
Loeffler bacillus. 

We have no certain notion as to the geographical 
origin of diphtheria, and may say with Trousseau that 
it is met at all seasons and under all climates. While 
formerly known mostly as as epidemic disease, it is 
to-day endemic in most of the great cities, and pre- 
vails much oftener than formerly in the country. 
Diphtheria generally appears in an epidemic form. 
In a country where this disease has seldom or never 
before been known, it first attacks a few isolated sub- 
jects, then spreads, multiplies its victims, and finally 
becomes extinct, only to reappear later. Generally 
the contagion has been brought by a patient or by in- 
fected objects from some locality where the disease 
had been prevailing. In other cases, there is a sort 
of reawakening of germs left in the locality by a 
previous epidemic — germs which had long remained 
inoffensive. 

Whether the disease be epidemic or endemic, it is 
transmitted by contagion. Just here a nice question 
arises: Is contagion indispensable to the development 
of the disease ? In other words, may a healthy sub- 
ject be attacked by diphtheria without taking the 
specific germ from a person afflicted with the disease ? 
We cannot at present give a positive answer to this 



question. In studying, farther on, the pseudo-diph- 
theritic bacillus of Loeffler, we shall see that there 
exists a bacterium which, not yet differentiated mor- 
phologically from the bacillus of diphtheria, is dis- 
tinguished only by the absence of virulence. Now 
this bacterium is found very frequently in the saliva 
of healthy persons, and some have been disposed to 
identify it with the Klebs-Loeffler bacillus, which 
may also remain inoffensive in the organism until 
quickened into virulence by some unknown stimulus. 
We have here an hypothesis similar to that which 
tends to confound the Bacterium coli communis, a 
microbe constantly present in faecal matters, with the 
bacillus of Eberth, the pathogenic agent of typhoid 
fever. If this notion should be established, our mode 
of conceiving of the origin and manner of develop- 
ment of infectious diseases would have to be materi- 
ally modified in many points. While waiting for such 
proof we may limit ovrselves by noting that observa- 
tion demonstrates the importance of contagion in 
most cases. 

The contagion of diphtheria may be transmitted 
either directly or indirectly. The direct method of 
contagion is no longer disputable, whether it be 
brought about by immediate contact or by inocula- 
tion. Persons who have the care of a diphtheritic 
patient are often contaminated by the saliva or false 
membranes which the patient ejects; in this way the 
medical attendant or nurse may contract diphtheria. 



' — 13 — 

But indirect transmission is much more frequent. 
Those who attend the patient (nurses, relatives, or 
physicians) are oftener the carriers of the contagion, 
which adheres to their fingers or their clothing. Physi- 
cians have even communicated it by unclean bistouries 
or tongue-depressors. Books and playthings, as well 
as articles of clothing, have carried the specific germ. 
Children have taken the disease by riding in a coach 
previously used to convey a diphtheritic patient home 
or to the hospital. Food, even, may contain the 
bacilli; milk has more than once been the vehicle of 
contagion. If the contagious element is not very 
diffusible, nevertheless dried particles of false mem- 
brane may be wafted in the dust, and, being inhaled 
at a distance, may thus impart the malady. In Zurich 
the streets are thoroughly swept on certain days 
(Wednesdays and Saturdays) and the dirt-carts re- 
move the rubbish; on these days Klebs has noticed 
an unusual number of cases of diphtheria to take 
their start, following, as it were, in the wake of the 
sweepers. 

Is diphtheria always of human origin? Do we 
not meet in certain animals, as pigeons, hens, cats, 
hares, and even cattle, pseudo-membranous affections 
which may communicate diphtheria to man? A 
number of writers admit this source of contagion, 
basing their opinion on the coincidence of certain 
epidemics of human diphtheria with pseudo-mem- 
branous affections of domestic animals. For a similar 



— 14 — 

reason some have affirmed the propagation of diph- 
theria by dung-heaps. It must, however, be admitted 
that all the bacteriological researches seem to demon- 
strate that these pseudo-membranous affections of 
fowls have for origin microbes different from the 
bacillus of Loeffler. 

At what epoch of the disease is diphtheria con- 
tagious? Possibly before the appearance of false 
membranes; but it is so at the highest degree when 
the false membranes are present, and eminently so 
during convalescence when the diphtheritic products 
are cast off. We know too that the saliva, when the 
false membranes are gone, may still contain the ba- 
cillus with all its virulence. Naturally, at such times, 
the occasions for contagion are abundant, for the 
patient will have returned to his ordinary mode of 
life. 

If the resistance of the diphtheritic bacillus is 
relatively feeble in the living organism, and if it cannot 
preserve its virulence longer than one or two months in 
a person convalescing from diphtheria, it has a longer 
vitality under other circumstances. The contagion 
may cling to objects of bedding, of furniture, etc., 
and keep all its virulence for years, as numerous 
examples prove. An instance in point is related by 
Sevestre. In a village of Normandy, in other respects 
healthy, a lad 14 years of age was attacked by diph- 
theria; and several days later a number of cases broke 
out in the village. In investigating the cause of this 



— i5 — 
epidemic, Dr. Legrand remarked that the houses in 
which successively appeared the cases of the disease 
were situated by the side of two roads which con- 
nected the several parts of the village; but he could 
not explain how the first case originated, for there 
had been no diphtheria in the region for twenty- 
three years. Several days before the outbreak, the 
grave-digger had dug up the ground in the parts of 
the cemetery where the children had been buried 
twenty-three years before, and had even handled the 
bones; in this work he had been assisted by his son, 
who was the first to be attacked with diphtheria about 
a week afterwards. 

Diphtheria is a disease of childhood, met most 
frequently between the ages of two and five years; it 
is rare in the new-born and in adults; very exceptional 
in the aged. It is a disease of winter, of damp, chilly 
weather. Certain local predispositions favor its ap- 
pearance. It is certain that persons affected with an 
acute or chronic inflammation of the throat, hyper- 
trophy of the tonsils, ulcerous lesions of the nose, 
lips, mouth, are more likely than persons not so 
affected to contract diphtheria. A first attack gives 
no exemption or immunity against another. Among 
the conditions which put the organism in a state of 
receptivity, we may mention the eruptive fevers, 
puerperality, defective hygienic conditions, unclean- 
liness, poverty with its attendant miseries. 

To cause diphtheria, the Loeffler bacillus must 



— 16 — 

come in contact with an excoriated mucous membrane 
or cutaneous surface, thus prepared for the inocula- 
tion; fixing itself there, it provokes the development 
of a false membrane, in which it lodges; there it lives 
and multiplies, remaining in the most superficial strata; 
it lives always outside of the organism, which it poi- 
sons by the toxine which it secretes. This is not 
all. If Loeffler's bacillus is necessarily present in the 
false membranes, there are other micro-organisms 
associated with it, some of which are pathogenic and 
may modify the course of the disease by producing 
secondary infections. 

We must study the bacillus, the poison, and the 
secondary infections of diphtheria. 

[The statement that the Klebs-Loeffler bacillus 
never penetrates the mucosa, nroer invades the glands, 
the internal organs, the blood, is contradicted by 
other authorities, notably Drs. Abbott and Ghriskey 
of the Johns Hopkins Hospital {vide the April, 1893, 
number of the Johns Hopkins Bulletin). In the same 
number of the Bulletin, Dr. Howard reports a case of 
ulcerative endocarditis due to the Bacillus diphtheria. 
Dr. Flexner also reports a case of diphtheria with 
broncho-pneumonia in which he found isolated diph- 
theritic bacilli in the broncho-pneumonic areas. — 
Translator.] 

The Diphtheritic Bacillus. — The most ready, 
the most simple, though at the same time the most 
incomplete, way of studying the bacillus of Loefner, is 



— i7 — 
to look for it in suitably stained microscopic prepara- 
tions of the false membrane. Bits of the exudate 
may be rubbed over the slides and stained, or sections 
may be made of the membrane hardened in alcohol. 
If the patient be a child, keep the tongue out of 
the way by a tongue-depressor; if need be, wedge the 
mouth well open. With a long curved forceps, catch 
hold of and remove a bit of the exudate, or remove it 
by means of a suitable well-sterilized swab. The in- 
struments, of course, must be thoroughly aseptic. 

If the examination is not to be made immediately, 
place the bits of false membrane in a sterilized test- 
tube, which should be closed with a plug of antiseptic 
cotton. When you are ready to make the examina- 
tion, scratch the surface of the false membrane with 
the point of a sterilized platinum wire, and smear sev- 
eral slides, which must then be dried, stained, and 
examined. If the exudation has been collected on a 
swab, rub the slides with it, and dry them by placing 
them on a sheet of blotting-paper, the surface contain- 
ing the preparation being turned upward. When it is 
sufficiently dried, pass the slide three times through 
the flame of an alcohol-lamp, the same side upward. 
Lastly, dip the slide into the staining fluid. There 
is nothing better than the alkaline solution of methy- 
lene blue, called Loeffler's blue: 

Saturated alcoholic solution of methylene blue, 30 Cc. 
Distilled water, 100 Cc. 
Caustic potash, 1 centigramme. 



It is better to extemporize this solution for each 
examination, and to employ it only when fresh. Keep 
in one bottle a solution of potassa (r: ioooo), and in 
another bottle a saturated alcoholic solution of 
methylene blue. At the moment of the examination, 
fill a watch glass with the potassa solution and add a 
few drops of the methylene- blue solution, till the 
surface of the staining fluid is no longer translucent. 
The glass slides must be withdrawn at the end of a 
few minutes and washed under a stream of filtered 
water. The preparation may then be wiped with a 
piece of woolen cloth and mounted. If you wish to 
preserve the slide, mount in Canada balsam. 

Gentian violet is a good staining fluid, or Roux's- 
blue, of which the composition is as follows: 

Aqueous solution (i per cent.) of violet dahlia, i part. 
Aqueous solution (i per cent.) of methyl green, 3 parts. 
Distilled water, enough to obtain a moderately blue tint. 

This solution does not precipitate, and keeps 
clear. It suffices to put on your prepared slide, after 
it is dried, a drop of this blue, and let it stain 
thoroughly the object; wipe off the excess of coloring 
matter with blotting-paper, and it is ready for the 
microscope. Use an immersion lens, and you will see 
that among all the bacilli of the false membranes the 
diphtheritic bacilli stain the most quickly and the 
most intensely. 

This bacillus presents itself under an aspect very 
much like Koch's, but it is twice as thick, the extremi- 



— i 9 — 

ties are rounded, sometimes pear-shaped; some rods 
appear strangled in places, others granular, because 
they take the staining unequally. Many are curved. 
In many points they are grouped in little masses. 

If in certain grave cases we meet these bacteria 
almost exclusively in the false membranes, gener- 
ally they are mingled with a great quantity of differ- 
ent microbes, all well stained. These are the habitual 
microbes of the mouth: large filaments of leptothrix, 
large micrococci, staphylococci, and streptococci, 
bacilli larger and longer than the diphtheritic ba- 
cillus, and others shorter and more stunted. It is not 
always easy in the midst of these bacteria to dis- 
tinguish the Loeffler bacillus, and it is very much to 
be regretted that we have not yet found for its detec- 
tion a method as sure as those which enable us to 
detect the bacillus of tuberculosis. 

When a false membrane has been placed in abso- 
lute alcohol, it becomes hardened at the end of a 
couple of days. Then we can make sections and 
stain with Loeffler's blue or by the method of Gram. 
We note, then, under the microscope the situation of 
the micro-organisms in the false membrane. In the 
most superficial layer, the farthest from the mucosa, 
are seen in great quantity numerous quite varied mi- 
crobes. Immediately below, but still quite far from 
the deeper portions of the false membrane, are the 
Loeffler bacilli, grouped in little characteristic masses 
in the fibrinous reticulum. 



In order to isolate and cultivate the Loeffler 
bacillus, you should select, if possible, a case which 
is toxic from the onset, with thick false-mem- 
branes; and, with a platinum wire, scrape from 
the pseudo-membranous patches in the throat the 
debris which you wish to sow and cultivate. You 
can obtain good cultures with fresh pseudo-mem- 
branous debris, in an aseptic test-tube. If not pre- 
pared to begin the culture at once, dry the false 
membranes on filter-paper, for the dried bacilli are 
endowed with great resistance. Then, when you are 
ready to sow the material, let the false membrane 
soak a short time in a little filtered water; then 
scratch off a bit of the false membrane with the point 
of a sterilized platinum wire — the wire should be 
rather large and stiff, so that you can scratch off 
quite a piece. With this wire you may sow three or 
four test-tubes filled with the serum. 

Serum is the best culture medium for the diph- 
theritic bacillus; it grows in all kinds of serum rap- 
idly and abundantly. Loeffler gives the preference 
to this medium; his formula is as follows: 

Serum of calf or of sheep, 3 parts. 
Veal broth, neutralized, 1 part. 
Peptone, 1 per 100. 
Glucose, 1 per 100. 
Sea-salt, ^ per 100. 

But the blood-serum of horses or cows yields good 
results. By a daily exposure, of two hours' duration, 



to a temperature of 5 8° C. in the dry-heat stove, 
repeated for five consecutive days, sterilization is 
effected; then an elevation of the temperature to 70 
C. will accomplish gclatizination. Or the blood- 
serum of ascites or of pleurisy may be employed, 
though I have found this culture medium to give less 
satisfying results. 

Place the tubes of serum in the dry stove at 37 C. 
Remove them at the end of eighteen hours. If the 
case be really one of diphtheria, the tubes will con- 
tain a great number of colonies, for in serum the 
Loeffler bacillus excels almost all other microbes in 
the rapidity of its multiplication. So that if the 
colonies are numerous, one may almost prejudge the 
nature of the disease, as tubes sown with exudates 
not diphtheritic present few colonies or none at all in 
the first twenty-four hours. The colonies of the 
Loeffler bacillus present the form of grayish-white 
spots, opaque in the centre, as large as the head of a 
pin. In the serum-tube first sown the colonies are 
not generally isolated, but by their grouping give the 
figure of a continuous streak; in other tubes, how- 
ever, especially the last sown, it is very easy to study 
them separately. 

There are a few other bacilli which form colonies 
in as short a time as the Loeffler bacillus. There is 
first a coccus that grows very well on serum; after 
twenty hours its colonies are very similar, as seen by 
the naked eye, to those of diphtheria, but after thirty- 



six or forty-eight hours in the stove they are less 
voluminous than diphtheritic colonies of the same 
age, and take, moreover, in ageing, a very character- 
istic yellowish tint. Other cocci form in serum, after 
the first twenty-four hours, colonies whose aspect is 
identical with those of the Loeffier bacillus; their colora- 
tion is not modified with time, but their development is 
slower than that of the microbe of diphtheria. Lastly, 
you will sometimes find a very large coccus which 
liquefies the serum. 

It is very evident that diagnosis cannot be safely 
established by a naked-eye examination of cultures; 
use a platinum wire to convey a minute portion of the 
suspected colony to the microscope for verification. 

To obtain a pure culture, charge the platinum 
wire with a new portion of the verified colony, and 
make streaks with this wire over a series of tubes of 
serum. For greater security, this fragment of the 
colony may be first diluted in the tube of sterilized 
bouillon, and a drop of this sown in the form of 
streaks upon serum. These tubes, placed in the stove 
at 37 C, give at the end of twenty-four hours colo- 
nies of which most, if not all, contain the Loeffier 
bacillus in a state of absolute purity. 

When the tubes of serum directly sown with the 
debris of a false membrane contain numerous colo- 
nies of Loeffler's bacillus, the existence of diphtheria 
may be affirmed; but if the colonies are very scanty 
— three or four in all, for example — it will be neces- 



— 2 3 — 
sary to have recourse to the inoculation of the ba- 
cillus in the guinea-pig, for possibly the specimen 
may be of the pseudo-diphtheritic variety. I shall re- 
turn to this point farther on. 

The bacillus of diphtheria is a rod, straight or 
curved, always immobile, almost as long as the 
tubercle bacillus and twice as thick; such is the 
aspect which it presents in recent cultures on serum 
or gelose. It then stains very well with Loeffler's 
blue. When the cultures are older, it takes the 
Loeffler stain more unevenly. Cultivated in bouillon, 
the bacilli of diphtheria are grouped in little masses, 
of which the rods are often arranged parallel to each 
other, and often present forms of involution just 
as in the false membranes of diphtheria — though they 
are shorter, more stunted, some are swollen at their 
extremities, pear-shaped or club-shaped. Their 
rounded extremities stain very strongly. But we are 
not dealing here with spores, for a temperature of 6o° 
C. suffices to kill all these cultures. 

In cultures on gelatin, the bacilli do not at all 
resemble the forms I have described; they are fusi- 
form, roundish, resembling large cocci. Moreover, 
transported from the gelatin or bouillon to serum, they 
assume the aspect which they usually present in these 
media. 

The diphtheritic bacillus stains well with anilin 
dyes, and particularly with Loeffler's or Roux's blue; 
it stains intensely by Gram's method. 



— 24 — 

In all media this bacillus develops badly below 
20° C, and not at all above 40 C. The most favor- 
able temperature is between 33° and 37 C. 

On gelatinized serum, at the end of eighteen 
hours the Loeffler colonies have the aspect which I 
have already described. Confluent, they form a gray- 
ish stria. Isolated, they present themselves under the 
aspect of little round spots, of grayish-white color. 
Soon they extend, become salient, with centre 
thicker than the periphery. At the end of four or 
five days they may attain a diameter of three to five 
millimecers, and are thick, whitish, opaque, with shiny 
surface. When the bacilli have been sown on serum 
prepared according to Loeffler's method, they grow 
still more quickly, for in two days a colony may ac- 
quire a thickness of one millimeter and a diameter of 
five millimeters. 

The cultures on gelose grow less rapidly than on 
serum, especially when the bacillus is taken directly 
from a false membrane; but the colonies present a 
characteristic aspect, they often spread considerably, 
and their contour is not perfectly round. They are 
white, the centre much thicker than the periphery, 
and take a grayish coloration when the cultures are 
sufficiently old. 

Veal broth constitutes an excellent culture medium 
for the bacillus. The cultures form little scales on 
the sides and at the bottom of the flask; the broth, 
after its first access of turbidity, regains its original 



— 25 — 
clearness, and when the cultures are kept in the stove 
at 37 C. a part of the colonies form a pellicle on the 
surface of the liquid. After several days of culture, 
the broth, first alkaline, becomes acid and continues 
so for a fortnight, then regains its alkaline reaction 
(/'. e., if exposed to free air; otherwise it continues acid). 

The bacillus does not develop on potato, and 
rapidly loses its virulence on glycerized broth (which 
soon becomes of exaggerated acidity) and in glycer- 
ized serum (which takes on an acid reaction not ob- 
served in ordinary serum). The bacillus grows in 
milk, and does not coagulate it. Pricked into gelatin, 
the development goes on poorly; little spherical col- 
onies adhere the one to the other along the track of 
the wire; at the end of a long time the cultures spread 
over the surface of the gelatin in the form of a thin 
whitish pellicle. 

Since the time of Bretonneau the attempt has 
frequently been made to inoculate diphtheritic mem- 
branes in animals, with the intent of reproducing the 
disease. The results obtained have not been conclu- 
sive. But from the day when the bacteriologist found 
out how to isolate the bacillus from the false mem- 
brane, with always the same characters as above de- 
scribed, and was able to cultivate it, innumerable 
attempts have been made to reproduce the principal 
features of the disease by means of inoculation with 
pure cultures of the specific microbe. The results 
have not been disappointing. 



— 26 — 

By excoriating the mucous membrane of the 
pharynx of hens and pigeons, the conjunctivae of 
hares, or the vulvar mucous membrane of the guinea- 
pig, and spreading over the excoriated surface por- 
tions of the colonies of Loeffler's bacillus by means 
of a platinum wire, false membranes are obtained 
quite like those which occur in man. They are also 
easily obtained by painting the blistered skin of a 
hare's ear with some of the culture-liquid. 

By inoculating in the same way with the diph- 
theria bacillus the trachea of hares or of pigeons 
previously tracheotomized, symptoms resembling 
croup are easily reproduced. The difficulty in 
breathing, the noise which the air makes in passing 
through the obstructed trachea, the aspect of the 
trachea congested and lined with false membranes, 
the cedematous swelling of the glands of the neck, 
render this resemblance actually striking. Death is 
very frequent after these inoculations; but when the 
animal resists, motor troubles may follow resembling 
the diphtheritic paralysis of man. 

By injecting one cubic centimeter of diphtheria 
culture in the marginal vein of the hare's ear, one 
often produces similar paralysis, should the animal 
live long enough. Sometimes it is a rapid paralysis 
extending to the whole body, and fatal in a few hours; 
sometimes a paraplegia of the posterior extremities, 
invading the whole body in a day or two, and killing 
the animal by arrest of respiration and of the heart. 



— 27 — 

In animals thus inoculated, the autopsy generally 
reveals, along with fatty degeneration of the liver, 
swelling of the glands and congestion of the ab- 
dominal organs — an acute nephritis which explains 
the albuminuria noted during life. Lastly, in animals, 
as in the diphtheria of man, the bacillus poisons the 
organism and does not infect it. Loeffler has never 
found the diphtheria bacillus anywhere but at the 
point of inoculation. Roux and Yersin have multi- 
plied experiments to control this important fact. 
With one exception, that of the guinea-pig inoculated 
in the subcutaneous cellular tissue of the abdomen, 
they have never found the specific bacillus except in 
the oedematous fluid and false membranes which de- 
velop at the point of inoculation. When the bacillus 
is sown in the blood, in the visceral parenchyma, or in 
pleural effusions, the result is nil. Sixteen hours 
after the intra-venous injection of Loeffler's bacillus 
in the hare, no more trace of it is found in the blood 
or in the organs. And at the same time the disease 
pursues its course, and the animals under experimen- 
tation die in the course of thirty-six hours. 

To sum up: A bacillus has been isolated which 
is found constantly in the false membranes of diph- 
theritic patients. Inoculated in animals, it repro- 
duces false membranes identical with those of diph- 
theria, all the symptomatology of croup, paralysis, 
and albuminuria. This bacillus produces its effects 
first by an infection, which is and which remains 



— 28 — 

local, but it rapidly develops a general intoxication 
of the organism. And if it be objected that the rap- 
idly invading paralysis provoked in the hare resem- 
bles only a rare form of the diphtheritic paralysis, we 
may here anticipate the results to be studied later on 
in connection with the diphtheritic poison, and remark 
that Roux and Yersin have succeeded in producing in 
the dog limited paralysis with slow course, identical 
with that commonly observed in man as the effect of 
diphtheria. So many accumulated proofs forbid doubt; 
and bacteriolgy has completely triumphed in its con- 
tention of the specificity of Loeffler's bacillus. 

This bacillus is pathogenic to a great number of 
animals. Rats and mice are completely refractory. 
The guinea-pig is peculiarly susceptible; a few drops 
of culture-broth injected under the skin of the belly 
rapidly kill this animal. At the autopsy we always 
find these lesions: gelatinous oedema at the point of 
inoculation; false membrane more or less extensive 
over the place where the skin was pricked; conges- 
tion of the internal organs and of the glands, but 
especially of the suprarenal capsules; serous or sero- 
sanguinolent effusion in the pleural cavities; some- 
times splenization of the lungs. Blood from the 
heart and internal organs, or even some of the pleural 
exudation, will not yield cultures when sown on serum; 
but a fragment of the false membrane from the point 
of inoculation will produce a luxuriant growth. These 
bacilli may, moreover, be microscopically detected 



— 2 9 — 

immediately after the autopsy in the liquid or mem- 
brane obtained from the place of puncture. What is 
a little singular, the microbes will be much less abun- 
dant than in the false membranes of human diphthe- 
ria; the animal is, in fact, more refractory to the 
microbe than is man. A marked attenuation of viru- 
lence is noted in transmitting the diphtheria from 
guinea-pigs to other guinea-pigs. 

The death of pigeons and of hares inoculated 
under the skin is much less rapid and constant. 
Pigeons and hens resist more or less according to the 
virulence of the bacillus and the quantity of culture 
inoculated — in general, a fifth of a cubic centimeter 
of diphtheria culture is the maximum dose which they 
can support without succumbing. Pigeons which die, 
exhibit at the autopsy only oedema and a pseudo- 
membranous product at the point of inoculation, and 
congestion of the internal organs. 

On the contrary, little birds are of all animals the 
most sensitive to the action of the bacillus of diph- 
theria. 

It requires 2 Cc. of culture in broth to kill a 
hare by subcutaneous injection. The teguments be- 
come oedematous at the point of inoculation, the 
animal lies motionless, refuses food, and dies in four 
or five days; there is then oedema at the level of the 
prick, with hemorrhagic suffusions of the cellular 
tissue; glandular, omental, and mesenteric congestions 
are also observed, with little ecchymoses along the 



— 3° — 
blood-vessels, and always the characteristic lesion of 
the liver, the yellowish tint due to fatty degenera- 
tion. 

In the dog, which also succumbs to subcutaneous 
inoculation of the diphtheria bacillus, the same local 
oedema occurs at the point of injection; the animal is 
paralyzed, lies motionless, and presents the signs of 
an intense jaundice. The autopsy reveals sclerosis 
and extreme hypertrophy of the liver. 

Cats live six to thirteen days after inoculation. 
They succumb much more rapidly when inoculated 
with bacilli that have passed through guinea-pigs. 
The bacilli are found only at the point of inoculation. 

Similar experiments, with similar results, have 
been made on cows. 

The vitality of the Loefner bacillus, both in and 
outside of the organism, is very great, but diminishes 
in proportion as the patient advances toward re- 
covery. When the false membrane disaggregates, 
becomes softer, it is a sign that it is invaded by com- 
mon microbes, and that the specific microbe has dis- 
appeared. But it is exceptional that we observe the 
complete disappearance of the Loefner bacillus so 
long as the pseudo-membranous exudate lasts. 

The presence of the microbe of diphtheria in the 
mouth is not necessarily always accompanied by the 
presence of the pseudo-membranous production in 
the bucco-pharyngeal cavity. In a case of hyper- 
toxic diphtheria supervening in the course of typhoid 



— 3i — 
fever, in the service of Cadet de Gassicourt, it was 
found by serum-cultures that the mucus of the throat 
contained a great quantity of extremely virulent ba- 
cilli of diphtheria, while at the same time only a very 
small lenticular pseudo-membrane was discoverable, 
and this disappeared in the course of a few hours and 
was not reproduced; there was no croup. The diph- 
theria bacillus is found in the saliva of children af- 
fected with croup, where no false membranes have 
appeared in the throat. 

When the false membrane has disappeared, and 
the patient has recovered, often the specific bacil- 
lus may be found in the mouth for a week or more, 
and colonies obtained therefrom are virulent for 
animals inoculated. Hence convalescent patients 
may be a source of danger to persons who come in 
contact with them; it is not known how long after 
recovery this bacillary survival lasts. Researches 
thus far made have pertained to children treated in 
the hospital and subjected to rigid antisepsis of the 
mouth and throat. But we have no means of deter- 
mining the duration of the resistance of the bacilli in 
cases where this antisepsis has been imperfectly per- 
formed. Here is a field for future inquiry. Possibly 
in rare cases the bacillus may long remain a harmless 
tenant of the mouth, though awaiting a suitable occa- 
sion to initiate a recurrence of the malady. 

In serum cultures the bacillus lives much longer. 
Kept at the temperature of the room, the tubes may 



— 32 — 
show them active for more than six months. Cul- 
tures in bouillon, in closed tubes without air and away 
from the light, retain their vitality and their virulence 
for thirteen months. On objects of bedding, in the 
folds of garments, in the crevices of walls, in the dust 
of the floors, etc., the bacilli may remain in a dried 
state for an indefinite time, preserving all their viru- 
lence. Dried bacilli placed in a room at 33 C. (91 
F.) have remained virulent for three months; they 
may even support with impunity a dry heat of 90° C. 
(nearly the boiling-point) for over an hour. A natural 
inference from all this is the uselessness of dry heat 
as a means of disinfection in diphtheria. It is note- 
worthy that a bit of dried diphtheritic membrane 
folded up and put away in a closed drawer, and kept 
at the temperature of the room, will yield at the end 
of five months colonies of the Loeffler bacillus 
scarcely less abundant than in the first days. 

The destruction of diphtheritic virus is effected 
in various ways. It may be spontaneous, as in the or- 
ganism, where the bacilli disappear as the condition 
of the patient improves, or as in old cultures, where at 
the end of a certain time the bacilli, when sown anew, 
no longer give rise to cultures. Dried bacilli, kept at 
the temperature of 45 ° C. for five days, remain sterile. 
The desiccated false-membranes, the bacilli of which 
preserve their vitality for five months, at least, when 
they are kept away from moisture and light, give 
negative results when sown in culture media after 



— 33 — 
being exposed to the air, moisture and the sunshine 
for a month and a half. Sojourn for a few minutes 
in moist air at 58° C. always kills the bacilli, and this 
explains the good results in prophylaxis obtained in 
the hospitals by disinfection of garments, etc., under 
high steam-pressure. 

The destruction of the bacillus of diphtheria by 
antiseptic solutions is easily obtained. According to 
D. Espine, solution of corrosive sublimate 1:8000, 
of phenic acid 2: 100, of permanganate of potash 
1:2000, will immediately sterilize vigorous cultures. 
To determine the value of an antiseptic solution, 
Chantemesse and Vidal immerse sterilized silk threads 
first in a culture of virulent diphtheritic bacilli, and 
then for a few minutes in the antiseptic solution; 
then the threads are washed in distilled water to rid 
them of any traces of antiseptic substance that may 
cling to them, dipped into culture-tubes of pure bouil- 
lon, and placed in the dry stove at 37 C. These 
tubes remain sterile if the antiseptic solution is suffi- 
ciently strong. 

The mixture which has furnished the best results 
is the following: 

Phenic acid, 5 grammes. 

Camphor, 20 grammes. 

Glycerin, 25 grammes. 

M. Barbier has recently shown that sulphoricinat- 
ed phenol is still more efficacious. 

Unfortunately the results are not so speedy and 



— 34 — 
complete when we have to do with the human organ- 
ism infected with diphtheria, for it is by no means 
easy to reach the specific bacillus in all the anfractu- 
osities of the bucco-pharyngeal cavity. 

All the Loeffler bacilli obtained from the throats 
of diphtheritic patients are not endowed with the 
same virulence. This is easily proved by sowing, in 
broth, bacilli taken from a series of specific anginas,, 
and inoculating under the skin an equal portion of these 
liquid cultures in guinea-pigs of the same weight. 
These animals will not die at the end of the same 
time. The guinea-pig constitutes a good test of the 
virulence of the Loeffler bacillus. After keeping one 
cubic centimeter of a bouillon culture twenty-four 
hours in the stove, inject under the skin, and the ani- 
mal will succumb sometimes before the end of the first 
day, often at the end of two days, rarely surviving" 
longer. There will be found oedema and an eschar 
at the point of inoculation. The virulence can be 
measured if at the same time a guinea-pig, a pigeon, 
and a hare be inoculated, for the pigeon possesses a 
resistance to diphtheria greater than that of the 
guinea-pig, but less than that of the hare. 

In fatal diphtherias all the colonies that may be 
used for purposes of inoculation are very virulent; in 
the severe but not so malignant forms, the specific 
colonies become less numerous as the disease pro- 
gresses toward recovery — while the colonies of the first 
days are all virulent, later colonies are likely to be 



— 35 — 
less active, and some even inoffensive to the guinea- 
pig. In benign diphtherias a still greater inequality 
in the virulence of isolated colonies is to be observed, 
but as a general rule the bacilli are less active than 
in the more grave forms of the disease. Still, in a 
fairly benign angina very virulent colonies may be 
isolated; which again proves that the bacillus alone 
does not create the disease, but that we must make 
great account of the predisposition and of the second- 
ary infections. 

We have just seen that the Loeffler bacillus may 
normally in the organism present an attenuated viru- 
lence, whether in the course of benign diphtherias or 
at the end of more grave epidemics terminating in 
recovery. In these cases, instead of killing the 
guinea-pig inoculated under the skin in one or two 
days, it kills in four or five days, and sometimes even 
not at all, causing only a local and curable lesion. 
This is also sometimes the case when we inoculate 
very old cultures: the guinea-pigs die at the end of a 
long time, or even survive. But this is not a true 
attenuation, for to merit that name the latter should 
be hereditary; we cannot say of a bacillus that it is 
attenuated until when, sown anew, it gives a daughter- 
culture equally attenuated. Now by sowing these 
old cultures in broth, we may see them recover all 
their primitive virulence. At the same time, very 
exceptionally we discover a real spontaneous attenua- 
tion in the cultures. 



- 36 - 

Roux and Yersin have met with two examples 
in which the cultures, primarily very virulent, gave 
daughter-cultures of very feeble virulence. They 
have artificially obtained the attenuation of virulence 
both in the false membranes and in the cultures. 
For the false membranes they have employed the 
combined action of the air and of desiccation. A 
false membrane is taken from the trachea of a child 
at the moment of tracheotomy, spread out on a clean 
cloth, dried in the air, then kept in a drawer. This 
false membrane, when fresh, contains many bacilli 
easy to see under the microscope; sown in serum, it 
gives fine colonies; inoculated in guinea-pigs, it kills 
them in less than two days. A new sowing made at 
the end of the fifth month of desiccation furnishes 
colonies less numerous; pure cultures of these, inocu- 
lated in guinea-pigs, prove inoffensive — there is little 
or no oedema at the point of inoculation. 

In cultures the diphtheritic bacilli become at- 
tenuated when cultivated in a current of air at the 
temperature of 39°-4o° C, and very soon die. The 
cultures are made in bouillon by means of Fernbach's 
flasks, which have lateral tubes through which a cur- 
rent of air saturated with steam at the temperature of 
the stove is caused to pass. The vitality of these 
cultures is quite short, but before dying they lose 
their virulence. All the bacilli are not attenuated at 
the same time; during a certain period the culture 
contains both attenuated and virulent bacilli, as can 



— 37 — 
be proved by separating on serum a great number of 
colonies, and by testing the virulence of each; day 
by day the number of malignant colonies diminishes, 
while the non-malignant augment proportionally. 

When the bacillus of diphtheria has been attenu- 
ated to a point where it no longer provokes much 
reaction at the point of inoculation in the guinea-pig, 
it has thus far been found impossible to reawaken 
its virulence. Successive inoculations in very sensi- 
tive animals, which constitute for many microbes an 
excellent means of restoring to them their primitive 
activity, remain here without effect; for very young 
animals, guinea-pigs or hares, show themselves re- 
fractory to the first inoculation. But bacilli having 
still a slight action on guinea-pigs, associated in equal 
parts with a very active culture of erysipelococci, have 
reproduced in the guinea-pig the lesions of diphtheria; 
and serum-tubes sown with the serosity taken from 
the point of inoculation have yielded abundant col- 
onies of the Loeffler bacillus, killing the guinea-pigs 
in less than thirty-six hours. 



THE DIPHTHERIA-POISON. 

To explain the general symptoms characterizing 
intoxication by the microbe, we must recognize the 
fact before mentioned that the bacilli, which remain 
local and do not invade the economy to any extent, 
secrete a poison, and that the constitutional disturb- 
ances are not produced until this poison is absorbed. 
It is easy enough to isolate this poison by simply 
filtering cultures of the Loeffler bacillus through a 
porcelain filter with the apparatus of Kitasato. The 
bacilli remain on the filter; the poison passes through 
with the bouillon. The cultures ought to be at least 
fifteen or twenty days old, otherwise the bacilli will 
not have had time to develop a sufficient quantity of 
poison. Moreover, when you make use of cultures kept 
exposed to the air (in flasks stopped with cotton), you 
must wait till the bouillon becomes acid, then alkaline 
again. At that moment it contains a great quantity 
of diphtheria poison. As soon as the liquid is com- 
pletely filtered, take it up in a series of sterilized 
pipettes, which must then be sealed in the flame of 
the lamp, and placed for several days in the stove at 
37° C, in order to guard against infection of the 
filtered bouillon by other microbes from without or 
that may have passed through the filter. When the 
filtered culture is at least two or three weeks old, and 
one or two cubic centimeters are injected under the 
skin of guinea-pigs, the animals will die in a space of 



— 39 — 
time which varies from twenty-four hours to seven or 
eight days, according to the age of the culture, and 
consequently the toxicity of its poison. With very 
old cultures one-tenth of a cubic centimeter of filtered 
bouillon will kill a guinea-pig, so strong is the poi- 
son. One-fifteenth of a cubic centimeter will sicken 
guinea-pigs but may not kill them; they then present 
at the point of inoculation, oedema and quite exten- 
sive necrosis of the skin. At the autopsy the lesions 
are found identical with those produced by injection 
of the diphtheritic bacillus, only the false membrane 
at the point of inoculation is wanting. There is the 
•same local oedema at the point of the prick, the same 
congestion of the internal organs (and especially of 
the supra-renal capsules), the same effusion in the 
pleura. 

Doses of the filtered bouillon varying from i to 4 
Cc, in subcutaneous injection, cause the death of the 
hares in two, three, or four days. Here also the 
lesions are the same as those produced by the inocu- 
lation of the diphtheritic bacillus: local oedema, gen- 
eralized congestion, sanguineous suffusions, and espe- 
cially the characteristic fatty liver. 

A cubic centimeter of toxic bouillon introduced 
under the skin of the pigeon suffices to kill it. 

Mice and rats, immune toward the diphtheritic 
bacillus, exhibit the same resistance toward the poi- 
son. Two cubic centimeters of the filtered diph- 
theritic bouillon injected into a mouse will not even 



— 4Q — 

produce necrosis at the point of inoculation. If, 
however, the liquid be concentrated in vacuo, a very 
large dose in very small volume will kill the mouse. 
Roux and Yersin, in order to kill a white mouse, had 
to employ a dose sufficient to kill eighty guinea-pigs. 

The results which have been obtained by intra- 
venous inoculation of animals are very interesting. A 
fifth of a cubic centimeter of toxic bouillon introduced 
into the circulation of a hare suffices to kill the animal 
very rapidly. A less quantity is not so speedily fatal, 
but sometimes produces paralytic symptoms. After 
having received a larger dose than one cubic centi- 
meter, a dog succumbs more or less quickly. If he 
survives several days, he emaciates, is taken with 
vomiting, has icterus, and dies with cirrhosis of the 
liver and nephritis. 

When it is desired that dogs shall not succumb 
to the intoxication, it will not do to exceed for a 
medium-sized dog (seven to ten kilogrammes) a dose 
of three-fourths of a cubic centimeter for inoculation. 
The animal then emaciates, lies stupid and prostrated, 
and often at the end of eight to ten days presents 
symptoms of motor paralysis — a paralysis which is 
generally incomplete, sometimes affecting all four 
limbs, sometimes only two, the hind limbs or the fore 
limbs, and almost always extending to all four ex- 
tremities. After a short period of aggravation, often 
accompanied by trembling, the paralysis gradually 
diminishes, remaining for a time confined to one leg, 



— 41 — 
then disappears altogether. The paralysis generally 
lasts from three to four weeks. 

The filtered bouillon may with impunity be in- 
gested in great quantity by guinea-pigs and pigeons, 
while one-half of a cubic centimeter introduced into 
the trachea of pigeons kills them in four or five days, 
without any lesion of the respiratory organs. 

Such are the results obtained with filtered cul- 
tures of Loeffler's bacillus in bouillon. If you treat 
the filtered bouillon with chloride of calcium in 
moderate quantity, there forms a precipitate of phos- 
phate of lime, which, when collected on a filter and 
washed with care, proves to be very toxic, killing 
guinea-pigs and hares in three or four days by sub- 
cutaneous injection, with exactly the same lesions as 
those produced by subcutaneous injections of filtered 
bouillon. Hence the precipitated phosphate of lime 
carries down with it the diphtheritic poison. 

If you concentrate in vacuo filtered diphtheritic 
bouillon, and add six times its volume of alcohol, a 
precipitate forms which contains the poison; the latter 
is very soluble in water. Roux and Yersin have en- 
deavored to obtain the maximum of concentration 
possible of the toxic substance. To this end, they 
evaporated in vacuo one cubic centimeter of the active 
liquid, which gave one centigramme of dried residue. 
Reckoning out the weight of the ashes and the portion 
insoluble in alcohol which has no toxic action, there 
remains a weight of four-tenths of a milligramme of 



— 4 2 — 

organic matter. Although most of this is made up 
of substances other than the diphtheritic poison, this 
quantity nevertheless suffices to kill at least eight 
guinea-pigs weighing 400 grammes each, or two hares 
of three kilogrammes each, or to make very sick and 
even kill a dog weighing nine kilogrammes. 

The formation of the poison is favored by heat, 
i.e., the cultures which ordinarily take twenty days to 
elaborate their toxine may produce an abundance in 
a few days when exposed in Fernbach's balloon flasks 
to a heat of 55 C. (131 F.) and traversed by a cur- 
rent of air. On the contrary, the preservation of the 
toxine is better effected in closed vessels, sheltered 
from the air and light; in such .circumstances the fil- 
tered bouillon easily keeps all its toxicity five months. 

The conditions which hinder the formation of 
the diphtheria poison or destroy it completely are 
numerous. In contact with the air the toxic power 
diminishes little by little; and this action, which is 
very slow in the darkness, is hastened by solar light. 
Sunlight alone very slowly destroys the toxicity. 
Filtered bouillon is also modified by the action of 
heat. Kept two hours at 58 C. (136 F.) or twenty 
minutes at ioo° C. (212 F.), the filtered bouillon be- 
comes so modified that animals inoculated with the 
poison long survive, but in the end succumb, after 
considerable emaciation, marked cachexia, and par- 
alysis of the hind limbs, just like animals that have 
been inoculated with macerations of the organs or 



— 43 — 
with the filtered urine of diphtheritic patients. When 
calcium chloride is added to filtered bouillon, precipi- 
tating the poison by the phosphate of lime, it will be 
observed that the precipitate when dried in vacuo acts 
less quickly on the animals than does the wet precipi- 
tate; but, on the other hand, it long resists the action 
of the air, at a temperature of 70 C. (158 F.), and 
even a heat of ioo° C. (212° F.) in the sea-bath for 
twenty minutes. 

The diphtheritic poison may also be attenuated 
by acidifying a very toxic filtered bouillon. The 
poison is the more attenuated, the longer it remains 
in contact with the acid. The toxicity is almost com- 
pletely abolished by lactic or tartaric acid; it is 
diminished, but in less proportions, by phenic acid, 
boric acid, and borate of soda. 

The property which the bacillus possesses of pro- 
ducing the diphtheritic poison diminishes with diminu- 
tion of its virulence, attenuated cultures producing 
hardly any toxic substance. Behring and Katasato 
have shown that the poison is destroyed in the bodies 
of refractory animals. 

Authorities are not yet settled as to the chemical 
nature of this diphtheritic poison. Roux and Yersin 
think it to be a compound akin to the diastases. Like 
the latter, it is modified by heat or by air, and pre- 
cipitated by alcohol; it easily adheres to precipitates. 
It, however, differs from the diastases in remaining 
without action upon sugar and the albuminoids. 



— 44 — 
According to Brieger and Fraenkel, the poison 
is not a diastase, but a toxalbumin, resulting from 
the transformation by the diastase of the albumins of 
the nutrient fluid. They have isolated this toxalbu- 
min, and give the following formula: C 45 . 36 , H,. 13 , 

•N 16'33> ^1-39' ^29-80- 

Inoculated in hares and guinea-pigs, this toxalbu- 
min kills them in the dose of 2^ milligrammes per 
kilogramme of the weight of the animal. Sometimes 
death is delayed for weeks, and even months. The 
toxalbumin kept in a vacuum may preserve its viru- 
lence for several weeks. 

Wassermann and Proskauer have reached the same 
conclusions as Brieger and Fraenkel. They think that 
the toxalbumin of diphtheria is not a simple body, but 
that it contains two kinds of substances: first albu- 
moses, then the diphtheritic poison properly so-called 
united mechanically (not chemically) to these albu- 
moses and endowed with the property of undergoing 
precipitation with them. This is the secret of the 
variations observed in the toxicity of the matters des- 
ignated as toxalbumins, which are found more or less 
charged with poison, according to circumstances. The 
toxalbumin isolated by the German chemists is, then, 
an exceedingly complex body, containing probably 
great quantities of substances absolutely foreign to 
the poison itself, since the dried precipitate obtained 
by Roux and Yersin is a hundred times more toxic to 
animals than the toxalbumin of Brieger and Fraenkel. 



— 45 — 

Gamelei'a puts forth a new conception, viz., that 
the diphtheritic toxine is derived from certain constit- 
uents of the bodies of the specific bacilli. This author 
attempts to show by the action of the soluble fer- 
ments on this poison that it is decomposable into two 
substances, one of which produces cachexia in the 
animals. The reactions place this cachecticizing 
poison among the nucleins; the primary poison is 
only a nuclein-compound, it is a nucleo-albumin. 

Quite recently, Guinochot, cultivating the Loef- 
fier bacillus in urine free from albuminoid matters, 
and inoculating guinea-pigs with cultures filtered 
through porcelain, showed that the animals under ex- 
perimentation died with the same lesions as the con- 
trol guinea-pigs inoculated with a culture in bouillon, 
and that consequently the toxine of diphtheria is not 
necessarily derivable from albuminoid matters, as 
affirmed by the German chemists. Moreover, it 
seems that the toxine itself cannot be an albumin in 
these conditions, for one cannot find in culture-urine 
any trace of albuminoid matters by the ordinary 
reagents (Tanret's test, the biuret test, etc.). 

Several attempts have been made during the past 
few years to render animals immune to diphtheria. 
Already in 1887 Hoffman had observed that guinea- 
pigs inoculated with old cultures spontaneously atten- 
uated remained refractory to inoculation with recent 
cultures certainly virulent. Fraenkel and Brieger 
have shown that by inoculating guinea-pigs with ten 



_ 4 6 - 

to twenty cubic centimeters of diphtheritic culture 
bouillon three weeks old and heated between 65 ° and 
70 C. for one hour, the animal is rendered refractory 
to subcutaneous inoculation alone. The immunity is not 
acquired during the first few days which follow the 
protective inoculation, for at this time an inoculation 
of a virulent culture would be more rapidly followed 
by death than if there had been no previous inocula- 
tion. It is only at the end of a fortnight that the ani- 
mal may receive under the skin the virulent bacilli of 
diphtheria. Moreover, if animals be inoculated with 
the Loeffler bacillus, and immediately or after a few 
hours again inoculated with cultures heated to 65 
and 70 C, the subjects die more rapidly than other- 
wise. These authors contend that the diphtheritic 
bouillon contains two principles: a toxalbumin which 
loses its virulence at 70 C, and a second substance 
that can withstand higher temperatures and is capa- 
ble of conferring immunity. 

These results do not involve any therapeutic ap- 
plication. I shall only mention the tentatives of vac- 
cination of diphtheria practiced on animals and even 
on children by Ferran; they were far from being suc- 
cessful. But this is not the case with the experiments 
of Behring. This savant has succeeded in conferring 
immunity on animals by different processes: (1) by 
the method of Fraenkel and Brieger, just stated; (2) 
by inoculating the animals several times with cultures 
of diphtheria containing constantly decreasing doses of 



— 47 — 
trichloride of iodine; (3) by using the pleural exudate 
found in the cadavers of animals dead of diphtheria; 
(4) by injecting either trichloride of iodine, or chlo- 
ride of gold and sodium, in animals already inocu- 
lated with the Loeffler bacillus; (5) by making sub- 
cutaneous preventive injections with oxygenated 
water, and then inoculating with the diphtheritic 
germ. Behring has injected the blood of a guinea- 
pig thus immunized into the peritoneum of other 
guinea-pigs; he has been able by this means not only 
to confer imnunity — and an immediate immunity — 
but he has also succeeded in curing animals pre- 
viously inoculated with the Loeffler bacillus. He has 
also remarked that this preservative and curative ac- 
tion of the blood of animals that have acquired immu- 
nity is not permanent, but diminishes with time. He 
thinks that the blood of immunized animals has 
no microbicide but only a toxicide action; which 
suffices to explain its effects. In any event, the short 
duration of the immunity confeired shows plainly that 
we are not here dealing with a true vaccination, and 
thai the blood of immunized animals has no other 
properties than those of an antitoxic substance. 

Behring has quite recently published a new 
method of vaccination. The diphtheria bacillus cul- 
tivated in bouillon made from calves' thymus pro- 
duces a very feeble toxine. To prepare this bouillon, 
take two or three fresh thymus glands, hash them 
fine, and add an equal quantity of distilled water; 



- 4 8 — 

macerate twelve hours in a refrigerator; strain and 
express carefully. Add to the filtrate equal weights 
of carbonate of soda and distilled water in quantities 
sufficient to prevent precipitation in heating up to 
ioo° C. for fifteen minutes. After this the liquid be- 
comes grayish-brown; then filter anew through linen 
to remove the woolly-like flakes that form; pour into 
culture-tubes, and sterilize in the autoclave. Sow 
this bouillon with the virulent Loeffler bacillus. 
When the toxine is well developed, heat the culture 
up to 65 or 70 C. for fifteen minutes. By this 
means you eliminate the toxic principle, and there 
remains only the vaccinant principle. Then inject 
into the peritoneum of a guinea-pig 2 (two) Cc. of this 
heated culture. This injection is to be repeated two 
days afterward, and then at the end of four days. 
Nine days after the vaccinant injections, the gumea- 
pig is inoculated with one milligramme of a very vir- 
ulent diphtheritic culture, and resists the inoculation, 
but at the point where the injection was made there 
will be oedema, then an eschar, in which is found the 
living diphtheria bacillus. This demonstrates that 
the immunizing injections have, strictly speaking, an 
antitoxic, but not a vaccinant, property. 



SECONDARY INFECTIONS IN DIPHTHERIA. 

We know that in most diseases, to the primary 
infection provoked by the specific microbe are added 
secondary infections due to the intervention of other 
pathogenic bacteria. These bacteria thus contribute 
to a transformation of the disease, whether by pro- 
voking local troubles at the point of inoculation, or 
by distant complications, or by infecting the entire 
organism through the circulation, or by poisoning the 
economy by the toxines when they develop. 

It cannot be said, however, that we have yet 
isolated and studied all the microbes which are met 
with in the false membranes along with the Loeffler 
bacillus. Several evidently are pathogenic, but re- 
searches have thus far pertained to only a few of 
them. We know that the Strepto-occiis pyogenes is 
found very frequently in the false membranes of the 
diphtheritic. It is not likely to remain confined to 
the part affected, but may pervade the entire organ- 
ism through the blood, or find a lodgment in some 
distant point. Its association with the Loeffler ba- 
cillus may be expected to give rise to the hypertoxic 
forms of diphtheria, veritable septicaemias, in which 
the microscope shows the presence of the streptococ- 
cus in the blood of every part. This streptococcus is 
found in a state of purity in the suppurations which 
sometimes accompany diphtheria. It has been found 
in the otites, the adenites, the phlegmons of the neck, 



- 5° — 
the suppurations of the trachea consecutive to trache- 
otomy, the arthrites, and even in mediastinitis accom- 
panied with pleurisy and pericarditis. This microbe 
has been especially studied in diphtheritic broncho- 
pneumonias, where it has been found associated with 
the Talamon-Fraenkel pneumococcus, and where it 
seems to play the principal role. It has also been 
detected in the vegetations of endocarditis superven- 
ing in the course of diphtheria. Lastly, it may give 
rise to a grave erysipelas, which will make the prog- 
nosis sufficiently gloomy. 

Not so well known is the role of the staphylococ- 
cus {aureus and albus) which has also been found in 
the false membranes and in the air-passages and lungs- 
affected by broncho-pneumonia, along with a certain 
number of cocci not yet classified. 

This is about all that we know as to the second- 
ary infections of diphtheria; and I shall have finished 
this division of the subject when I have said that the 
Loeffier bacillus confers no exemption from the con- 
tagion of measles, scarlet fever, and whooping-cough. 



THE PSEUDO-DIPHTHERITIC BACILLUS. 

In his first researches on the bacillus of diphtheria, 
Loeffler found this bacillus with all its morphological 
characters in the saliva of a healthy child. In a 
second memoir, he describes a bacillus found in the 
pseudo-membranous products very like the specific 
bacillus, but differentiated by certain characters of its 
cultures, and especially by the absence of all patho- 
genic action on animals. Since then, this bacillus has 
been well studied by Hoffmann, Zarniko, and espe- 
cially by Roux and Yersin. When several tubes of 
gelatinized serum are sown in streaks with false mem- 
branes, especially if these are taken from a case of 
benign diphtheria, we sometimes find in the midst 
of numerous colonies of very virulent bacilli one or 
more colonies which produce no effect on animals by 
inoculation. If you sow on serum in the same manner 
mucus taken from the throats of patients affected 
with anginas not diphtheritic (rubeolic angina espe- 
cially) you will sometimes observe in one of the tubes 
sown (and generally in not. more than one) several 
rare colonies of bacilli offering all the characters of 
the diphtheritic bacillus except its virulence. Inocu- 
lated in animals, they are inert.* 



* Among the distinctive features of this pseudo-diph- 
theritic bacillus is its rarity. Out of several tubes sown 
with diphtheritic membrane, you will find scattering colonies 
<>f the pseudo-bacillus in only one or two; in the sore-throat of 



— 5 2 — 
The pseudo-diphtheritic bacillus stains like the 
virulent bacillus by the Loeffler blue, by Roux's blue 
compound, and by the method of Gram. When the 
process is examined under the microscope, it will be 
seen that the bacilli undergo the staining uniformly, 
or else appear granular, the staining matter having 
an elective action upon certain points. The bacillus 
is a rod, straight or curved, with roundish (sometimes 
swollen) extremities, quite like the diphtheria bacillus, 
but (according to Loeffler) not quite so long. Sown 
on serum at 37 C, the pseudo-diphtheritic bacillus 
yields vigorous colonies, growing as quickly and pre- 
senting the same appearance as those of the specific 
bacillus. On gelose the aspect of the colony is 
identical with that of the diphtheritic bacillus, but 
there is difference of growth which is sufficiently 
marked, especially at a moderate temperature, in 
favor of the former. When cultivated in bouillon, 
the pseudo-diphtheritic deposit is thicker and whiter 
than that of the virulent bacillus, and the bouillon 
remains alkaline instead of becoming acid (Zarniko). 
Roux and Yersin dispute this latter point; both ba- 
cilli, they say, render the bouillon acid, then alkaline, 
but the change of reaction is more speedy in the case 



measles, it is seldom that these bacilli are found in any 
abundance, and the inoculation test shows them to be rela- 
tively harmless. Recently Ortmann found this pseudo-diph- 
theritic bacillus in a case of purulent meningitis associated 
with the pneumococcus. 



— 53 — 
of the pseudo-diphtheritic bacillus. The cultures of 
the latter on gelatin at 20 C. are more abundant than 
those of the Loeffier bacillus, and the latter grows 
more abundantly in a vacuum than the former. 

Moist heat kills the pseudo-diphtheritic bacillus 
at 68° C. in ten minutes; just as it does the Loeffier 
bacillus. Animals the most sensitive to the diphther- 
itic virus resist inoculation with the former; nothing at 
the most is seen but a little oedema at the point of in- 
oculation in guinea-pigs; the most marked cedemas 
being caused by the bacilli from rubeolic anginas. 
Likewise inoculation by its filtered cultures is gener- 
ally inoffensive, though large quantities cause emaci- 
ation and finally death. 

Many authorities admit, with Loeffier, that the 
inoffensive bacillus is very similar to the virulent bacil- 
lus. They base their differentiation on the points I 
have mentioned: the pseudo-diphtheritic bacillus is 
shorter, cultivates more vigorously and at a lower 
temperature in different media, and grows more spar- 
ingly in a vacuum; if its cultures in bouillon at a 
given moment present the acid reaction, this reaction 
lasts but a short time; lastly, neither the bacillus nor 
its filtered cultures are found virulent to animals. 

These differences do not seem to Roux and Yer- 
sin sufficient to carry conviction. They say they have 
seen the benign bacilli yield, for the first few days, 
cultures as poor as those of the virulent bacillus. 
Moreover, abundance of culture has never sufficed to 



— 54 — 
characterize a microbe. The morphological differ- 
ences are so feeble that they prove nothing. There 
remains the question of virulence. But these authors 
have carried on the attenuation of virulent cultures 
placed at 40 C. in a current of air, and these cultures 
became inoffensive to animals, whereas previous to 
attenuation they would have been sure death. Nay, 
more, these attenuated bacilli take on in cultures the 
characters of the pseudo-diphtheritic bacillus; they 
grow better than the virulent form in the air and at 
a low temperature, and not so well, on the contrary, 
in a vacuum. Lastly, when a large quantity of their 
filtered culture is injected into guinea-pigs, these ani- 
mals grow thin and cachectic, sometimes even die at 
length — a result just like what we get with massive 
doses of the filtered culture of the pseudo-diphtheritic 
bacillus. 

The demonstration would be complete if Roux 
and Yersin had succeeded in rendering virulent the 
pseudo-diphtheritic bacillus. Unhappily, all their 
tentatives in this direction have been in vain. De- 
spite this failure, they are disposed to affirm the iden- 
tity of the two bacilli. " Under the influence of an 
eruptive fever or of some unknown microbian associ- 
ation, the pseudo-diphtheritic bacillus takes on viru- 
lence and becomes the active diphtheritic poison. 
This is only a hypothesis; but as we have proved that 
the virulent bacillus of diphtheria may be attenuated 
so as to be indistinguishable from the pseudo-diph- 



— 55 — 
theritic, it is not unreasonable to suppose that this 
pseudo-diphtheritic bacillus plays a role in the etiology 
of diphtheria. It is still very difficult to define the 
role. Most cases of diphtheria are surely due to 
direct contagion, whether by means of fresh or of 
dried virus; but alongside of these diphtherias coming 
directly from a virulent bacillus, there probably exist 
some which have for their origin this pseudo-diph- 
theritic bacillus, parasite of so many mouths. Becom- 
ing virulent through conditions which we cannot yet 
explain, it may be the starting-point of new conta- 
gions. The idea that a saprophyte microbe may be- 
come pathogenic has been introduced with authority 
into science by the experiments of the laboratory of 
Pasteur on the attenuation of virus and its return to 
virulence. It was set forth in a note by Pasteur, 
Chamberland, and Roux in 1881; since then it has 
been accepted by many savants, and we think it a 
fruitful notion which explains many facts otherwise 
inexplicable." 



FALSE DIPHTHERIAS. 

Writers have long discussed the nature of certain 
pseudo-membranous products which objectively are 
confounded with the diphtheritic false-membrane, but 
differ by the concomitant symptoms and by the course 
of true diphtheria. Such is the grayish exudate which 
is found on inflamed wounds and ulcers, on blisters 
badly treated, on patches of intertrigo that have been 
irritated; such are the false membranes of the so- 
called diphtheritic form of puerperal fever, the pseudo- 
membranous products which sometimes extend over 
the infectant chancre or secondary syphilides, those 
which cover the lips of children affected with measles, 
which supervene in the course of simple anginas, and 
especially at the onset of scarlatina. 

Bacteriology alone can settle any doubt in this 
matter by showing that these false membranes do not 
contain the Loeffler bacillus. It is probable that 
there are several bacteria capable of provoking fibrin- 
ous exudations which undergo organization into false 
membranes. Among these are the golden and white 
staphylococci, the streptococcus pyogenes, and the 
Talamon-Fraenkel pneumococcus. Experimentation 
has shown that with the streptococcus pyogenes found 
in puerperal diphtheroid patches, in certain anginas 
with suspicious pseudo-membranous exudates, and in 
the early pseudo-diphtheritic anginas of scarlet fever, 
we may succeed in reproducing false membranes of 



— 57 — 
considerable extent and toughness upon the excoriated 
mucous membrane of the beak of pigeons. I have 
also isolated the staphylococcus aureus from the 
white, thick patches adherent to the stomatitis of 
patients suffering from measles. Lastly, I have found 
the pneumococcus in pseudo-membranous angina and 
laryngitis. 

All these affections, where the Loeffler bacillus 
is wanting, merit the name of false diphtheria. With 
diphtheria they have nothing in common but the 
false membrane, and they are distinguished by the 
absence of the characteristic intoxication which the 
specific bacillus produces. We shall study them more 
completely in connection with the diagnosis of diph- 
theria. 

6 uuu 



ANIMAL DIPHTHERIA. 

There exists in several species of animals, notably 
in birds, a disease characterized by a false membrane 
very like that of human diphtheria. This sometimes 
appears in the trachea, causing asphyxia, with stridu- 
lus breathing similar to that of croup. This aviary 
diphtheria is believed by some writers to be identical 
with the malady as found in man. These writers 
point to the frequent coincidence of epizootic pseudo- 
membranous diseases among fowl with epidemics of 
diphtheria among men, and the undeniable fact of 
the experimental infection of pigeons and other birds 
by the Loeffler bacillus, the ensuing malady exhibit- 
ing the main features of the disease as it prevails 
naturally among birds. But these statements of con- 
tagion have been disputed, and numerous instances 
in contradiction have been given. Let us see what 
data we actually possess respecting animal diph- 
theria. 

Competent observers have noted pseudo-mem- 
branous affections in birds, cattle, hares, cats, sheep, 
and hogs. The diphtheria of birds attacks chiefly 
pigeons, hens, pheasants, and some wild birds. It is 
epidemic and contagious; is often met with in barn- 
yards and henneries, where it decimates the fowl; is 
characterized by false membranes about the beak, 
mouth and throat, the nares, the larynx, and some- 
times the intestine. The malady may localize itself 



— 59 — 
in one patch, or may spread and even invade the 
entire mucous tract. There exists a visceral form 
of this affection, with fibrinous deposits resembling, 
at first sight, miliary tuberculosis. You may even re- 
produce all these forms by applying to the different 
mucosae the virulent matters of aviary diphtheria. 
The most frequent and best known form is that com- 
monly called the pip. This exhibits grayish false- 
membranes covering the tongue, throat, nasal fossae, 
and finally obstructing these passages by its exuber- 
ance. When this exudate is removed, the mucosa is 
seen to be eroded underneath; but the false mem- 
branes are speedily reproduced. The bronchi or the 
conjunctivae may be secondarily invaded. On pal- 
pating the cutaneous surface, you often discover little 
fibrinous nodules. This disease often lasts days, 
weeks, and even months. 

Megnin has described a latent form of the diph- 
theria of pigeons, in which the adult birds preserve 
all the appearances of health and have only little 
diphtheritic pellicles in the oesophagus, but may 
transmit a fatal diphtheria to their young. The 
prognosis is grave, without being necessarily hopeless. 
There are numerous little cutaneous tumors contain- 
ing a yellow fibrinous matter of caseous aspect. 
False membranes invade the conjunctivae, the nares, 
the trachea, and even the intestine. Below the exu- 
date, there is congestion of the mucosa and infiltration 
of the subjacent parts. 



— 6o — 

Aviary diphtheria attacks young birds especially, 
it is transmissible to other animals, notably cats. 

The specific microbe of aviary diphtheria is a rod 
resembling that of human diphtheria, but somewhat 
shorter, with extremities not swollen. It grows on 
gelatin at 17 or 18 C, and does not liquefy the 
gelatin; its colonies spread widely on the surface of 
the gelatin. On potato it gives a thin, grayish cul- 
ture. Loeffler inoculated four pigeons with this ba- 
cillus; he obtained inflammation at the point of inocu- 
lation, and a false membrane. Two of the pigeons 
died, and the bacillus was found in the lungs and 
liver. This bacillus is less active than that of human 
diphtheria in the hare, the guinea-pig, and the dog. 
Injected into hens, it produces only lenticular spots at 
the point of injection, without general empoisonment. 
Hence Loeffler thinks that the diphtheria of hens is 
not identical with that of pigeons. 

These researches have been confirmed by Babes, 
Puscariu, and Krajewski. 

Recently Haushalter isolated from the false 
membranes of hens affected with diphtheria, a ba- 
cillus which he considers as the specific agent of 
aviary diphtheria. Morphologically this bacillus re- 
sembles that of tuberculosis, but its length is variable. 
It does not liquefy gelatin. On gelose at 37 C. it 
forms a membranous elevation, white and smooth. It 
develops well at 37 C. on gelatinized serum; and 
gives rise to a grayish, moist, elevated papule on 



— 6i — 

potato at 37 C. The sown bouillon rapidly becomes 
turbid, and deposits a powdery sediment. 

The injection of these cultures into the blood of 
the hare, provokes diarrhoea and fever; the animal, 
however, recovers. Subcutaneous injection of the 
bacillus provokes suppuration. Inoculated in the 
pectoral muscle of a pigeon, it kills in less than forty- 
eight hours, and the bacillus is found in the blood. 
This bacillus is also pyogenic to hens. 

Bovine diphtheria is quite common in Germany, 
though unknown in France. It constitutes veritable 
epizootic epidemics. The animal is taken with ex- 
treme lassitude, with fever and prostration, has rigors, 
refuses to eat, and rapidly emaciates. There is an 
abundant flow of saliva; the snout is wide open; the 
tongue hangs out of the mouth and is almost always 
swollen. The swelling extends to the whole of the 
buccal mucosa, which is covered with yellow patches 
of exudation penetrating deeply into the mucosa, 
which is often eroded. These false membranes often 
have a thickness of one and a half centimeters. The 
pituitary, laryngeal, and tracheo-bronchial mucosae 
may be invaded in their turn; then there is a yellow- 
ish discharge, the respiration is labored and stertor- 
ous; there is sometimes pneumonia or pleurisy. The 
exudate is seen on the conjunctiva, in the interdigital 
space, and about the sheath. Often the animals 
are affected with pseudo-membranous enteritis, which 
manifests itself at first by constipation with hard 



— 62 — 

faeces covered with false membranes; then diarrhoea 
sets in, sometimes dysentery, almost always followed 
by death. The laryngo-pharyngitis, though less fatal 
than the enteritis, kills not less than four animals out 
of five. At the necropsy you will note cedematous 
infiltration below the mucous membrane which is 
covered with false membranes, and pseudo-membran- 
ous nodules in the skin, cellular tissue, muscles, liver, 
and lungs. The latter are often hepatized, some- 
times gangrenous. 

The virulent agent of this disease 'exists in the 
false membrane, the nasal discharge, and in the diar- 
rhceal liquid. With these products a pseudo-mem- 
branous affection may be provoked in calves, birds, 
hares, and sheep. .Loeffier has examined the false 
membranes of the buccal cavity in seven cases. On 
preparations stained with alkaline methylene blue 
the superficial stratum stains strongly with blue; be- 
low this there is a large zone unstained; then the 
deep layer forms a colored band. The first stratum 
contains a great variety of micro-organisms, especially 
cocci; in the deep part are seen bacilli united in long 
undulating filaments. These bacilli measure half the 
length of those of charbon; Loeffier considers them 
specific in bovine diphtheria. 

There exists in cats a disease characterized by 
dysphagia, inflammation of the palate and throat, and 
dyspnoea. The conjunctiva is sometimes red. The 
animals emaciate, cough, and have bronchial catarrh. 



_ 6 3 - 

Most cases recover, but the disease may last a long 
time. In one case there was paralysis of the hind 
limbs. Klein says the disease is transmissible to man. 
He found false membranes in the trachea and bronchi 
in three cases. Sections of this exudate stained 
showed in only one instance bacilli resembling the 
Loeffler bacillus; in the other two cases, where death 
was late, he found no bacillus. Sowings on various 
culture-media remained sterile. These facts are 
clearly insufficient to identify human diphtheria with 
the diphtheria of cats. 

Ribbort has studied in the hare a disease which 
produces acute fibrinous peritonitis, with swelling of 
the mesenteric glands, and characterized chiefly by 
the lesions of pseudo-membranous enteritis in the 
large and small intestines. He has isolated from the 
false membrane a bacillus 3 to 4 pi long and 1 to 1 /< 4 
broad, which grows well in gelatin without liquefying, 
and forms grayish colonies on agar and on potatoes. 
Subcutaneous inoculation of this bacillus determines 
a sort of septicaemia in the hare; in the throat it 
develops false membranes on the tonsils. 

In dogs there is often a sort of pseudo-membran- 
ous angina or stomatitis which is very grave, with 
fever, dysphagia, flow of saliva, and general enfeeble- 
ment; death supervenes at the end of five or six days. 

Hogs are also subject to a pseudo-membranous 
affection. 

These affections have not yet been studied from 
a bacteriological point of view. 



SYMPTOMS. 

Incubation. — When the Loeffler bacillus has 
penetrated the economy, before its presence is mani- 
fested on the mucous or cutaneous surface by local 
symptoms, and before its toxine has given rise to 
general symptoms, a variable time intervenes during 
which the infection remains latent; this is the incuba- 
tion period. Statistics prove that the duration of 
incubation is generally from one to three days, but 
exceptionally from twelve to fifteen days. Experi- 
ments on animals have indicated that the time which 
elapses between inoculation and the first manifesta- 
tion of the disease is proportionate to the quantity 
and virulence of the virus injected. It is probable 
that the soil on which the infection develops, and the 
resistance of the organism, play an important role, of 
which it is still impossible to measure the value. 

Clinical Study of Diphtheria. — We know 
now how the Loeffler bacillus acts on the organism; 
it fixes itself and forms colonies on the eroded mu- 
cous membrane or denuded derm, and produces a 
false membrane there, where it lives confined, devel- 
oping and multiplying outside of the organism. To 
these local manifestations are joined general acci- 
dents, functional troubles of organs remote from the 
point of infection. No one has ever found the Loef- 
fler bacillus in the blood or viscera; we must then re- 
fer these general disorders to the systemic poisoning 



- 65 - 

by the products of the diphtheritic bacillus, and to 
similar infections by other pathogenic bacteria whose 
association complicates the disease or may even com- 
pletely alter the clinical aspect. We know that the 
diphtheritic poison penetrates the circulation; it is 
easy to demonstrate this, for the urine of the patients 
contains a notable proportion of this poison; and if 
we inject this urine in animals we produce in them 
lesions identical with those which are consecutive to 
inoculation with the Loeffler bacillus or with the 
filtered bouillon. This poison fixes itself in most of 
the organs — the liver, the spleen, the kidneys, the 
heart, the nervous system, etc.; for a maceration of 
these organs injected into guinea-pigs and hares kills 
them, with all the lesions characteristic of diphtheria. 
It is certainly to the toxine that we must refer the 
alterations noted in these organs in diphtheritic pa- 
tients, for no bacteria are found there. This is not 
the case when certain complications exist, such as the 
suppurations, the broncho-pneumonias, which are often 
superadded to the diphtheria; we have seen that these 
owe their origin to new infections by microbes other 
than the Loeffler bacillus. 

It will be convenient to consider this subject 
under three heads: the first comprises the symptoms 
of bacillary infection; the second, those of systemic 
poisoning; thr third, the complications due to second- 
ary infections. 

Diphtheria sometimes begins by local, sometimes 



— 66 — 

by general, symptoms. In the latter case, the Loeffler 
bacillus has already been multiplying in an infected 
point, but has not yet produced the false membrane. 
Often, also, the disease is announced by symptoms at 
once local and general. The onset may be sudden, 
with great gravity, or slow and insidious. In chil- 
dren it is not rare to see diphtheria begin suddenly 
with a high fever, with a temperature of 40 C, and 
often with chills, vomiting, delirium, and convulsions,, 
lividity of the skin, etc.; and it may be only accident- 
ally that attention is directed to the throat. 

I. Symptoms of Bacillary Infection. — Diph- 
theria manifests itself by the development of a 
false membrane, at first thin, whitish, opaline, of 
rather softish consistence. This membrane may be 
seated on a mucous membrane or on any part of the 
skin; it is met with, in order of frequency, in the 
throat, larynx, nares, trachea, bronchi, mouth, Eus- 
tachian tube, middle ear, conjunctiva, prepuce, glans 
penis, anus, scrotum, and uterus; is extremely rare in 
the oesophagus, stomach, and intestine. In the sta- 
tionary period of the disease, the false membrane is 
firm and elastic; may generally be detached in large 
flakes with an ordinary swab or with forceps. Below, 
the mucosa or derm is rarely ulcerated, but bleeds 
easily. If a removed shred of the pseudo-membrane 
be agitated in a glass of water, it will not dissolve. 
The false membranes form at points where they give 
rise to little lenticular concretions, or oftener to exten- 



- 67 - 

sive circular patches or strips. Often they take the 
form of the organ on which they rest: the larynx, the 
Eustachian tube, etc. Exceptionally they have been 
known to take on extraordinary dimensions— in one 
instance, covering the skin from the neck to the sacrum. 
At first smooth, they soon become rugous; their sur- 
face is grayish, sometimes yellowish, or it may be 
brown, colored by the blood, and resembling a gan- 
grenous eschar — in very grave forms the fetid odor of 
the latter is noted - the consistence being pulpy, and 
the exudates forming a putrid and sanious magma. 
When the diphtheritic patient recovers, the false 
membrane softens, disintegrates, and disappears. 

One of the principal characters of the false 
membrane is its ability to reproduce itself repeatedly. 
When it is removed, the mucosa underneath remains 
at first bare, but in the course of a few hours the 
fibrinous exudate is re-formed; and this process will 
go on as long as the disease lasts. The false mem- 
brane has also the property of being essentially in- 
vading; it rarely remains localized to the point where 
it first forms, but spreads to contiguous regions; 
starting in the throat, it ascends the nasal foss?e, or 
spreads downward into the trachea. 

The particular seat of the false membrane de- 
termines in some measure the concomitant local 
symptoms. Diphtheria usually begins with a sore 
throat. There is nothing at first to excite alarm: a 
little redness and swelling of the velum pendulum 



- 68 — 

and tonsils; a sensation of dryness in the throat (there 
is yet no false membrane —it is the congestive period). 
After a few hours the mucous membrane exhibits a 
thin coating of mucus, partly concrete, which soon 
changes into an opaline patch, half transparent, but 
little adherent; this is the false membrane. From 
the first, there is a notable engorgement of the sub- 
maxillary glands, which become larger as the disease 
progresses. The false membrane is first seen on one 
or both tonsils; it may invade the soft palate or 
uvula, or extend to the nasal fossae and larynx. The 
pain generally remains slight and supportable; but 
the dysphagia, which was scarcely noticeable at first, 
generally augments as the false membranes extend. 
The voice takes on a nasal twang. The respiration 
is a little oppressed when there is hypertrophy of the 
tonsils, and especially when there is coryza. 

At whatever point the diphtheria develops, it 
always presents the local symptoms of an ordinary 
inflammation, with this phenomenon superadded: the 
formation of a false membrane. But when the disease 
invades the air-passages, it adds a new element to the 
symptom-picture and a factor of gravity to the prog- 
nosis: the mechanical obstacle which the false mem- 
brane interposes to respiration. 

In most cases, croup is preceded by a diphthe- 
ritic angina, and supervenes upon the latter in the 
course of the first week of the disease; sometimes all 
the characteristic symptoms appear from the very 



- 69 - 

onset. In primary croup, the laryngeal symptoms 
appear in the midst of apparently perfect health, or 
follow a slight cold or catarrh of the bronchi. Excep- 
tionally, the croup is ascendant — the bacillus having 
primarily affected the bronchi. 

It is customary to describe three periods in the 
progress of croup: 

(a) Period of Invasion: The patient complains 
of a little pain in the region of the trachea, speaks in 
a hoarse voice, and has a loud, hoarse, barking cough. 
More rarely the onset is sudden, as in stridulous laryn- 
gitis; a child, only a little hoarse the evening before, 
is awakened in the middle of the night by violent 
attacks of a hoarse, resonant cough; quiet follows, 
but the respiration gradually becomes difficult and 
interrupted. This first period may last several days, 
but sometimes the paroxysms of suffocation come on 
at the end of several hours, or even at the onset. 

{b) These paroxysms characterize the second 
period; the voice and cough are extinguished; dysp- 
noea becomes constant, with frequent attacks of suffo- 
cation; the latter come on sometimes spontaneously, 
without apparent cause, but sometimes are excited by 
emotion. All at once, with pale face and wild, staring 
eyes, the child starts up in bed in the anguish of suf- 
focation—clings to the bed-post — and, with head 
thrown back and mouth wide open, dilates the thoiax 
to its utmost. Inspiration is whistling, convulsive, 
painful, prolonged; expiration generally slow and 



laborious. At times, the child in coughing clutches 
at its throat, as though trying to rid itself of the ob- 
ject that is causing suffocation; the countenance all 
the time becoming livid. The attack lasts ten min- 
utes or so, and may terminate in death. Oftener 
there is another period of calm, during which the 
breathing improves, the color comes back, but respi- 
ration still remains noisy and embarrassed, till a new 
attack sets in. 

Sometimes there are no paroxysms of suffocation, 
but the dyspnoea gradually and without intermission 
becomes worse and worse. The obstacle in the larynx 
hinders the entrance of air into the bronchi; so when 
the thoracic cavity dilates in inspiration, the intra- 
thoracic pressure falls; there is a sort of aspiration of 
the abdominal organs from below upwards; the epigas- 
tric hollow is strongly depressed, instead of project- 
ing as in the normal state (substernal suction). As the 
glottic cleft becomes more obstructed, inspiration will 
be attended by a second depression at the lower part 
of the neck above the sternal notch. 

This dyspnoea is sometimes temporarily relieved 
by the expulsion of false membranes, which may show 
an exact moulding of the bronchial tree. Then the 
child becomes quiet and somnolent, and ceases to 
struggle against the asphyxia which is growing more 
and more pronounced. 

(c) The third period has now set in. The tegu- 
ments are cyanosed; the cheeks and lips are purple; 



— 7i — 
the extremities cold; the patient lies limp, inert, 
stupid, rousing from time to time when harassed by a 
paroxysm of coughing, then falling back and sur- 
rendering to the progressive asphyxia, and no longer 
responding to any excitation. This condition fre- 
quently yields to a state of complete resolution, very 
like coma; the patient may die suddenly in a parox- 
ysm of suffocation, or in convulsions. If, as rarely 
happens, croup which has arrived at this period 
terminates in amendment and recovery, the cough 
becomes more noisy and more moist, the dyspnoea 
diminishes and disappears, but the voice remains long 
husky. 

We shall see further on, that croup does not have 
the same aspect in the adult as in the child. 

Even in benign diphtheria it is a common thing 
to note a little coryza with serous discharge. But 
only in the malignant forms is there invasion of the 
nasal fossae by the false membrane; there is then red- 
ness of the nasal mucous membrane (which is covered 
with crusts), and a sero-mucous flow, often fetid and 
sanguinolent, which excoriates the skin of the upper 
lip; false membranes cover the turbinated bones. 
The specific bacillus may pass from the nares into the 
nasal duct, and the pseudo-membranous exudate in- 
vade and close the latter, producing a persistent flow 
of tears. The inner angle of the eye is soon invaded, 
and the false membrane spreads over the conjunctiva. 
Ocular diphtheria is, however, quite rare. 



— 72 — 

At the anus, vulva, or meatus urinarius, the 
medical attendant will sometimes notice diphtheritic 
patches, which generally appear secondarily to a 
diphtheria of the pharynx. Excoriated parts of the 
skin, lips, and nares, the surface of wounds (espe- 
cially those of tracheotomy), burns, leech-bites, etc., 
may be the seat of false membranes. Whenever, in 
fact, in a diphtheritic patient, you see an erosion of 
the skin, you should close it immediately by an anti- 
septic dressing. You cannot be too careful, especially 
in children, in the employment of sinapisms, for if you 
obtain a blistered surface you have a new seat of in- 
fection to deal with. When diphtheria invades the 
skin, the excoriated surface first becomes red, then is 
covered with false membranes. Phlyctenular appear 
around the infected point, break, and in turn become 
covered with false membrane. Often the affected 
parts take on a gangrenous appearance. The de- 
nuded derm also absorbs the diphtheritic poison, just 
like the mucous membrane when invaded by the dis- 
ease. 

II. Symptoms of Systemic Poisoning. — From 
the onset, unless the form of diphtheria be very benign, 
it is easy to see that the entire organism is smitten. 
The fever, the extreme pallor (often leaden hue), the 
general enfeeblement, the glandular engorgement, the 
albuminuria, the haemorrhages, are so many proofs 
that the poisoning follows close on the infection, 
while the myocarditis and the nervous troubles which 



— 73 — 
later supervene demonstrate that the poison survives 
the bacillus. 

In the gravest forms the patient lies apathetic, 
shows an invincible repugnance toward food, and ex- 
presses by his features and his aspect extreme lassi- 
tude and profound prostration. 

The fever is always variable and presents but 
few indications; is not, in fact, a characteristic symp- 
tom. In grave forms it may be nil, and in the most 
simple cases (even at the onset) extreme. Hence a 
high fever at the beginning should not alarm; has not 
a long duration, and does not cause depression of the 
forces. Generally in the first few days the tempera- 
ture does not exceed 38.5 or 39 C. — that is, it is 
lower than in an ordinary quinsy sore-throat. It is 
also rare to note chills at this period. 

During the stationary period the temperature 
varies according as the disease advances toward recov- 
ery or death ; if the former, the fever persists for several 
days, then the temperature suddenly or after several 
oscillations falls to the normal; a fatal termination, 
on the other hand, is generally preceded by a rising 
or permanently high temperature — exceptionally, how- 
ever, the temperature falls below the normal, when 
the extremities become cold and cynosed and the 
patient succumbs in complete algid collapsus. If any 
complication supervenes, the temperature remains 
elevated or rises again; such ascensions are observed 
when the false membrane is reproduced or grafts itself 



— 74 — 
on a new point, or when there is broncho-pneumonia, 
albuminuria, or paralysis. 

The pulse line is more regular than that of the 
temperature; in general the pulsations are frequent — 
1 20 to 140 per minute— and often do not become 
slower until the temperature has returned to the nor- 
mal. The more malignant the form of the disease, 
the more weak and rapid the pulse, though it may in 
some cases be abnormally small and slow. 

The acceleration of respiration is proportioned 
to the rise of temperature. 

The glandular engorgement is constant in diph- 
theria. The submaxillary, parotid, and supra-hyoidean 
glands are the most markedly swollen. The glandular 
tumefaction corresponds to the degree of intoxication; 
it develops early; the glands are taken singly or in 
groups; their size varies from that of a hazelnut to 
that of a walnut; they are painful to pressure, and 
the skin over them is a little hot and sometimes red. 
In the malignant forms the glandular engorgement 
takes on extraordinary proportions; there are then 
regular diphtheritic buboes; the cellular tissue which 
surrounds them is infiltrated and blended with the 
inflammatory mass so that the region is completely 
deformed. If the cervical glands are the seat of the 
engorgement, the tumefaction is so considerable that 
the neck appears larger than the head which it sup- 
ports. These adenopathies may suppurate by reason 
of a secondary infection by the pyogenic microbes. 



— 75 — 

The urine is generally scanty and high-colored, 
depositing urates copiously; in some cases, however, 
it is clear and transparent. The average urinary ex- 
cretion in cases that recover is 300 to 400 grammes 
in the twenty-four hours; in fatal cases the quantity 
may fall below 100 grammes, and there may even be 
complete anuria. Tracheotomy is generally followed 
by diuresis for two or three days. The density of the 
urine is always high, without, however, exceeding 
1.028 in favorable cases. 

Urea is augmented, and rises to 12 and 15 
grammes per liter, instead of 10; but in cases that 
terminate fatally the figure may fall to one gramme 
per liter. 

The urine in diphtheria is albuminous in more 
than two-thirds of the cases. Albumen may be found 
from the onset, or, as is oftener the case, from the third 
day — during all the stationary period, or at the end 
of the disease. Sometimes its disappearance coexists 
with a new development of false membranes. Albu- 
minous urine is generally limpid, of an amber-yellow 
color, rarely bloody. The deposit examined under 
the microscope reveals lithates and phosphates, epi- 
thelium, hyaline or fibrinous casts, and red and white 
blood-corpuscles. The quantity of albumen varies 
from a few centigrammes to ten grammes per liter. 
The albuminuria may be of brief duration, disappear- 
ing after twenty-four hours, or it may be persistent, 
even 1 ontinuing a month or two. The abundance of 



— 76 - 

the albumen is generally proportioned to the gravity 
of the diphtheria, but there is no fixed rule about this. 
Albuminuria in this malady may be looked upon as 
an epiphenomenon, which may in a certain measure 
indicate the degree of intoxication of the organism. 

It is rare to see diphtheritic patients present 
symptoms testifying to a profound renal lesion. The 
anasarca accompanying the albuminuria is quite ex- 
ceptional. There may be only a little oedema about 
the face. Sanne cites a case of oedema limited to the 
glottis, suggestive of croup. Uraemia is infrequent; 
when supervening, it takes on the eclampsic or coma- 
tose form. 

The digestive functions are not disturbed at the 
onset. Later on, the anorexia becomes absolute and 
constitutes a serious danger. Vomiting is a rather 
rare symptom; at the onset or prodromic period it 
is without gravity, but later it is almost a certain sign 
of serious complication. During convalescence, re- 
peated vomitings are of unfavorable omen and are 
often followed by a fatal termination. The vomited 
matters sometimes (though rarely) contain false mem- 
branes from the stomach or oesophagus. 

Diarrhoea coming on at a late stage is generally 
related to a marked degree of intoxication. The 
stools are then fetid and sanguinolent, sometimes 
containing the debris of false membranes. The pro- 
fuse diarrhoeas often noted in toxic diphtherias have 
been compared to the diarrhoea observed in hares 



— 77 — 
after intravenous inoculation with large quantities of 
the diphtheritic poison. 

Haemorrhages are tolerably frequent in diph- 
theria, and are almost always associated with malig- 
nant cases. It is especially at the onset that they 
have been noted, and during the first five or six days. 
I refer here to the dyscrasic haemorrhages which are 
dependent on a profound intoxication of the organism. 
They take place around the false membranes, the 
latter being thereby infiltrated and stained brown; 
the bleeding increases after swabbing the diphtheritic 
patches. The epistaxis of the prodromal period is 
sometimes very abundant; there is often spontaneous 
bleeding from the gums, lips, throat, and even pur- 
pura hemorrhagica has been noted. Haemorrhages 
into the nerve centres have been the cause of instant 
death or hemiplegia. The prognosis of haemorrhage 
in diphtheria is very grave. 

Cardiac and nervous disturbances characterize 
the convalescence. (Edema without albuminuria, 
general or limited to the face or extremities, has been 
observed from the eighteenth to the twentieth day of 
the disease. The pathogeny of this oedema is very 
obscure. 

When the local symptoms of diphtheria have all 
disappeared, and the patient is convalescent, some- 
times an attack of syncope supervenes, which is the 
first grave symptom of a complication previously 
latent: myocarditis. This lesion generally manifests 



- 7 8 - 

itself five, six, or eight days after the onset of conva- 
lescence — sometimes a little later, especially in young 
children. The first symptoms are: occasional palpi- 
tations, a little restlessness and dyspnoea, frequent 
pulse, a state of temporary cardiac erethism; then 
the pulse becomes feeble, compressible, and soft; the 
heart-beats are obscure and distant, with intermit- 
tences, and there is pain in the cardiac region. In 
adults this pain may be so severe as to simulate 
angina pectoris. Most of these symptoms may be 
overlooked in children until pallor and collapse sud- 
denly supervene. This pallor and cardiac failure are 
exaggerated on making effort, and the patient is 
always menaced with syncope. The general enfeeble 
ment continues; vomiting and diarrhoea are sometimes 
present. The precordial pain augments and becomes 
agonizing and constrictive. Children do not, how- 
ever, complain of this pain so much as adults, for 
children soon fall into collapse. Whatever may be 
the age of the patient, he is soon the prey of a very 
marked paroxysmal oppression; lies prostrate, with 
face livid, features pinched, lips cyanosed; then sud- 
denly he grows paler, and lies motionless — syncope 
has taken place. 

The pulse is irregular and compressible, with 
occasional intermittences; the feebleness of the pul- 
sations marks the insufficiency of the ventricular 
impulse. 

The physical signs obtained by examination of 



— 79 — 
the heart are those of acute dilatation. The precor- 
dial region presents a slight vaulting; you can see the 
propagation of the cardiac pulsations from the apex 
to the epigastrium. The apex is generally found in 
the fifth or sixth intercostal space, outside of the 
mammary line. The hand, instead of being raised by 
a single snock, perceives a series of successive undu- 
lations and irregularity of the shocks. Percussion 
indicates an augmentation of the volume of the heart 
in every direction; but it gives little information in 
the infant. Auscultation reveals all the types of 
arythmia possible, with more or less marked obscurity 
of the sounds of the heart. You may observe tachy- 
cardia, bradycardia, a bruit de galop, or reduplication 
of the second sound. Sometimes the first bruit is 
also reduplicated, and you hear four consecutive 
bruits. Inversely, one of the two bruits, especially 
the first, may be wanting. 

The state of the heart has been compared to that 
in animals poisoned by digitalis. As the enfeeble- 
ment of the cardiac muscle augments, there arises a 
soft systolic bruit, loudest at the apex, essentially 
transitory. This sign is found in most of the acute 
myocardites. Lastly, the sounds of the heart become 
more and more muffled and distant, until only a feeble 
undulation is perceived, which Lancisi called trem- 
bling of the heart. 

Along with these symptoms of cardiac enfeeble- 
ment the general prostration arrives at its maximum. 



— 8o — 

The teguments are ashy pale, covered with a cold 
sweat, the extremities cyanosed. The patient lies 
motionless, the respiratory movements scarcely per- 
ceptible. From the onset of the cardiac accidents, 
albumen reappears in the urine, but the temperature 
never transcends the normal, and may fall below it in 
a period of collapse. 

Thus it is that diphtheritic myocarditis comports 
itself: insidious, sometimes fulminant in the child, it 
follows a progressive course in the adult, who often 
survives one or perhaps several attacks of syncope; it 
is, nevertheless, almost always fatal. 

Generally from eight to fifteen days after re- 
covery from the local symptoms of diphtheria, the 
paralysis manifests itself. It may make its appear- 
ance earlier, even during or at the end of the first 
week; then again, it may come on as late as a month 
or two after the patient has apparently recovered. 
The rule is that the paralysis comes on during full 
convalescence. It is a very common accident of the 
disease — existing, according to Roger, in one-third of 
the grave but not fatal cases. 

The paralysis may follow the most benign as 
well as the most severe cases. There have been 
epidemics in which it was a very marked and almost 
always fatal symptom. It is not so common in 
children under ten years of age as in adults. 

The onset of the paralysis is generally slow and 
insidious. There is first only a little hesitation of the 



— Si — 

motor functions, then deglutition, walking, and other 
movements become more and more difficult. The 
paralysis may be ushered in during convalescence by 
a little febrile rise, or a return of albuminuria. 

The point of election of the paralysis is the velum 
pendulum, where it almost always begins, and where 
it may remain localized; or it may extend to other 
parts and constitute the generalized form of the dis- 
ease. 

When localized in the soft palate, the paralysis is 
essentially insidious. A slight pallor, a little slowing 
of the pulse, are the only disturbances of the general 
state which are noted. The paralysis would easily 
pass unperceived if the reflux of liquid aliments by 
the nasal fossa; did not indicate the impediment to 
deglutition. During the second stage of deglutition, 
the pharynx contracts on the alimentary bolus to 
seize it and propel it downwards; normally the velum 
pendulum falls back and closes the posterior nares, 
but when this muscular septum is paralyzed a por- 
tion of the ingesta will enter the nasal fossa;. 
There is generally at the same time a slight paresis 
of the upper part of the larynx; the occlusion of the 
glottis is incomplete, and the patient coughs during 
deglutition because a few drops of the liquid or par- 
ticles of food come in contact with the mucosa of the 
larynx. 

If the paralysis of the velum pendulum is com- 
plete from the onset or becomes so subsequently, if 



— 82 — 

the pharynx is paralyzed in its turn, the food can 
only be swallowed after repeated attempts, which 
soon fatigue the patient and sometimes lead him to- 
refuse all nourishment. The voice is feeble and 
nasal, the articulation of sounds difficult, the speech 
slow; and if the breathing is normal while the patient 
is awake, it is more or less stertorous during sleep. 

When the diphtheritic paralysis does not remain 
localized, it may begin with the velum pendulum, 
then extend to the muscles of the eyes, of the upper 
and lower limbs, of the trunk, of the neck, of the rec- 
tum and bladder, to end with the organs of the special 
senses. This is the ordinary course of the more com- 
plete forms of paralysis. More rarely, it may attack 
the lower limbs before affecting the larynx and the 
tongue, or even begin with the upper extremities, 
then invade the velum pendulum and pharynx, and 
lastly attack the lower limbs. 

When the paralysis is thus extensive, grave gen- 
eral symptoms — such as the ashy hue, collapse, rest- 
lessness—are often present; sometimes vomiting, se- 
vere diarrhoea, convulsions, and sooner or later coma. 
But these alarming symptoms are only met with in 
the very grave cases; and with the exception of a 
little albuminuria and fever at the onset, the constitu- 
tional symptoms may be inconspicuous. 

We shall follow, in the description of the troubles 
of motility, the usual order of extension of the paraly- 
sis. Generally affecting the entire surface of the soft 



- 8 3 - 

palate, it may be localized and only occupy one-half of 
this organ and the pharynx. If you titillate the base 
of the tongue or pharynx, you will see contractions 
on the side that is not paralyzed. The anaesthesia fre- 
quently extends to the upper part of the larynx, and 
this favors the passage of the food particles into the 
air-passages. 

After the velum pendulum, the muscles of the 
eyes are very often attacked. The muscles of ac- 
commodation are paralyzed; the motores oculorum 
are affected in their turn, and strabismus (which is 
sometimes temporary) and ptosis of the upper lid are 
noted. But generally troubles of vision, referable to 
a fault of accommodation, supervene; the sight is en- 
feebled in different degrees, from slight amblyopia to 
complete blindness; there is hypermetropia, mydriasis, 
and, if but one eye is affected, inequality of the 
pupils. Almost all of the ocular muscles may be in- 
volved in turn. 

The lower extremities may be paralyzed immedi- 
ately after the velum pendulum, and sometimes the 
paralysis is limited to this double manifestation; 
oftener they begin to be enfeebled when there already 
exist ocular troubles. The paralysis of the lower ex- 
tremities generally takes on the form of an incomplete 
paraplegia. It is announced by formications and 
numbness in the legs. Walking becomes uncertain; 
the patient has an incomplete perception of the 
ground under his feet, and finds it especially difficult 



— 8 4 - 

to go up and down stairs; darkness aggravates these 
troubles of motility. Then the muscular feebleness 
augments, and walking becomes very difficult if not 
impossible; at the same time, the paralysis is never 
complete. The patients, who are still able to stand, 
move along by dragging or sliding their feet, as though 
they were fastened to the ground by an enormous 
weight. When they are confined to bed, the lower 
limbs still retain considerable power of movement, 
but without energy or much reliability — Jaccoud 
calls it rather an ataxia of movement than a paralysis. 
Brenner divides these phenomena of incoordination 
into three classes: (i) True ataxia, caused probably 
by a lesion of the centre of coordination of move- 
ment; (2) ataxic paralysis, characterized by paresis 
of certain groups of muscles of the limbs and by the 
more complete paralysis of other muscles; (3) true 
paralysis, which may attack equally all the muscles 
of the limbs, and which may be complete or incom- 
plete. These ataxic symptoms, joined to the abolition 
of the patellar reflex and to the eye-troubles, may 
give rise to a form of pseudo-tabes. 

Contracture is quite rare. 

The enfeeblement and even the abolition of the 
patellar reflex has been often noted. These modi- 
fications are seen from the onset of the paralysis, and 
often survive the latter for some time. 

The affected muscles present the reaction of de- 
generation; there is augmentation of the galvanic 
and diminution of the faradic contractility. 



- 8 5 - 

The hands soon become awkward and clumsy; 
the patients drop or upset objects that they attempt 
to handle; the upper limbs are seized with tremblings. 
Then the muscular enfeeblement augments; the 
dynamometer marks only a force of 20 kilogrammes 
instead of 50, and the patient finally becomes so help- 
less as to be unable to move himself in bed, or to 
feed himself. Here, too, we find the same enfeeble- 
ment of the reflexes, the same reaction of degenera- 
tion, as in the lower members. 

The muscles of the neck and face may be para- 
lyzed in their turn. The paralysis of the face is rare; 
it may be complete or incomplete, unilateral or bi- 
lateral; in the latter case the features remain motion- 
less, and the visage takes on a stupid expression, 
although there may be no intellectual trouble. The 
tongue, the lips, the cheeks, may be affected at the 
same time; the saliva flows continually from the 
mouth; the tongue is agitated with fibrillary tremors, 
and may even hang out of the mouth. The patient 
speaks with difficulty, and stutters; can neither blow 
-nor whistle. En resume, the paralytic troubles may 
be united so as to form the labio-glosso-laryngeal 
syndrome. 

Paralysis of the bladder and rectum is also ob- 
served. If the muscles connected with the spinal 
column are affected, the latter is curved forwards, or 
may be deviated laterally. 

In the case of paralysis of the vocal cords, there 
is complete aphonia. 



— 86 — 

The heart troubles may be limited to temporary 
palpitations, tendencies to fainting, to slight irregu- 
larities of the pulse, but at other times take on a very 
grave aspect and manifest themselves by precordial 
anguish, cardiac ataxia, slowing of the pulse, attacks 
of suffocation, and syncope. Henoch divides the 
cardiac paralyses into three groups: (i) Early paraly- 
sis, whose prognosis is very unfavorable; (2) cardiac 
paralysis with later, but sudden, onset, coming on, so 
to speak, in full health, and accompanied with con- 
siderable frequency of the pulse; (3) cardiac paralysis 
developing more slowly, when there already exist 
other paralytic phenomena; prognosis is less un- 
favorable. The symptoms of respiratory and cardiac 
paralyses may be united and give rise to bulbar crises, 
indicated by Duchenne under the name of "bulbar 
form of diphtheritic paralysis " The patient has 
crises of asphyxia, finally fatal, or he may be carried 
off by an attack of syncope. 

The troubles of sensibility are very frequent in 
diphtheritic paralysis. Almost always they attack the 
paralyzed regions; often, however, we note akinesis 
without anaesthesia. The most frequent alteration of 
sensibility is anaesthesia; exceptionally there is hyper- 
aesthesia, which is announced in the lower limbs by 
numbness and formication, and generally precedes the 
paralysis. Frequently the anaesthesia, when it exists, 
does not extend above the knees or elbows, but this 
localization is not constant, and the anaesthesia may 



- 8 7 - 

be generalized. It is sometimes accompanied with 
analgesia so complete that surgeons have been able 
to perform cutting operations without chloroform. 
The anaesthesia may affect the lips, tongue, and 
cheeks; and in rare cases the special senses of hear- 
ing, smell and taste have been abolished. The speech 
is often hesitating, stammering. 

A capital fact in diphtheritic paralysis, one that 
distinguishes it from all other paralyses by peripheral 
neuritis, is that there is no muscular atrophy; the 
paralyzed limbs always retain their normal aspect and 
volume. 

In very rare instances the velum pendulum is not 
affected, and the disease is localized in one muscular 
group without attacking other groups or other parts; 
■such are the cases where the paralysis takes on the 
paraplegic or hemiplegic form, or where it is limited 
to the eye muscles, to a forearm, a leg, the hands, the 
feet, the lips, the anus, or the muscles of the trunk. 

In the localized form the paralytic accidents may 
be essentially transient, and may disappear after a 
few days. In such cases the enfeeblement of the 
velum pendulum only manifests itself by a little dys- 
phagia; now and then a little liquid flows back 
through the nose, but the patient on the whole swal- 
lows well. This is what happens also after trache- 
otomy; the drinks flow back by the cannula for a day 
or two. 

The paralysis of the velum pendulum may last a 



— 88 — 

considerable time, but in general, when it remains 
limited, it is perilous only by the dangers of asphyxia 
to which it exposes the patient in the possible pas- 
sage of aliments into the air-tubes. When the par- 
alysis is generalized, its course is slow, lasting weeks 
or even months. Yet it is not rare to see the early 
paralysis disappear in a few days, to return during 
convalescence under a different form. Landouzy has 
described a form of diphtheritic paralysis whose 
course resembles that of the acute ascending paralysis 
of Landry, attacking successively the lower limbs, 
then the upper, as well as the muscles of the trunk, 
accompanied by bulbar accidents, and terminating 
rapidly in death without any trouble of sensibility. 
Some writers have regarded mobility and diffusion of 
the symptoms as characteristic of diphtheritic par- 
alyses; but though these attacks do sometimes pass 
from one limb to another, then return to the one first 
affected, such alternations are not the rule. If fre- 
quently the paralysis invades successively the differ- 
ent vital apparatus in the order which we have 
adopted for the symptomatic description, there is 
nothing fixed about it. When one organ is affected, 
no one can foresee which member will suffer next; 
nothing gives assurance as to the time that the 
akinesis is to remain fixed to one part, for the para- 
lytic phenomena sometimes present remissions and 
exacerbations which defy any prevision. 

The paralysis terminates in recovery more than 



eight times out of ten; in these cases, power of move- 
ment reappears first in the lower limbs, then in the 
throat, then in the upper members, the trunk, the 
viscera, the eye. Generally the organs paralyzed first 
are the first to recover. There is, however, no fixed 
rule even here, and it often enough happens that after 
having been the first affected, the velum pendulum is 
the last to resume its functions. 

When the termination is fatal, death may take 
place slowly, rapidly, or suddenly. If slowly, the pa- 
tient becomes cachectic and more and more feeble; the 
profound troubles from which he suffers are generally 
attributed to inanition, as he refuses to take food for 
fear of suffocation or of reflux by the nares. But it 
has been observed in these cases that feeding by the 
stomach-tube does not always suffice to save the pa- 
tient. The cachexia, therefore, must be referred to 
the diphtheritic poison. 

Writers have mentioned as occasionally occurring 
after diphtheria, nervous affections distinct from the 
diphtheritic paralysis: pseudo-membranous menin- 
gitis, of which three striking cases are on record; 
hemiplegia following cerebral hemorrhage; multilo- 
cular sclerosis; attacks of mania, of symmetrical 
asphyxia of the extremities, of hysterical paralysis. 
Lyonnet even mentions certain arthropathies of nerv- 
ous origin, a sort of trophic peri-articular affection 
supervening during convalescence from diphtheria. 



COMPLICATIONS DUE TO SECONDARY INFEC- 
TIONS. 

We have seen, in studying the secondary infec- 
tions of diphtheria from a bacteriological point of 
view, that the streptococcus pyogenes, often found in 
the false membrane associated with the Loeffler ba- 
cillus, may invade the circulation and infect the entire 
organism. It thus produces a general septicaemia 
which much modifies the clinical aspect of the dis- 
ease. 

Gangrene may invade the points attacked by the 
diphtheria. The parts subjacent to the false mem- 
brane soften; the latter becomes black, and gives off 
a fetid odor. The gangrene may extend in surface 
and in depth, and hasten the fatal termination. 

Suppurations are numerous, with multiple locali- 
zations; note the middle-ear otites, the glandular 
abscesses, the phlegmons of the neck, the perichon- 
drites of the larynx, the suppurations of the trachea, 
etc. Cutaneous suppurations, patches of impetigo, 
pustules of eczema, multiple whitlows, boils, frequently 
accompany diphtheria in children. 

Endocarditis is very rare; Sanne in 149 cases 
had not seen one with this complication. 

I have placed among the secondary infections 
the diphtheritic erythemata, because in his recent 
work Mussy attributes to the streptococcus their pro- 
duction in most cases. These erythemata resemble 



— 9 i — 
those met with in the false (streptococcus) diphthe- 
rias, and in puerperal fevers. (This pathogenic ex- 
planation demands further substantiation.) 

The frequency of these erythemata is variable — 
once in thirty cases, sometimes once in four or five 
cases. Adults are much more subject to them than 
children. They are early, appearing during the first 
week; or they may be late, and testify to a profound 
infection of the organism, to be certainly followed by 
death in a short time. The eruption appears in cer- 
tain favorite localities, about the wrists, elbows, knees, 
ankles, the upper part of the thighs; in general, it 
respects the face. 

Robinson describes two species of erythema 
appearing in the course of diphtheria; the one early, 
transient, apyretic, scarlatiniform, without desquama- 
tion; the other tardy, special to toxic diphtheria, mul- 
tiform, and rubeolic. 

Mussy describes a multiform erythema, lasting 
from one to four days, neither desquamative nor pru- 
riginous; a scarlatinifoi m non-desquamative erythema; 
a rubeolic erythema; and a purpuric ery hema, asso- 
ciated or not with a multiform erythema. Fraenkel 
considers the latter one of the most frequent eruptions 
of diphtheria. This variety may appear at the onset 
or at the end of the disease. It is constituted by 
little haemorrhagic spots whose size varies from that 
of a pea to that of the head of a fine pin. This erup- 
tion may easily pass unperceived. 



— 9 2 — 

Broncho-pneumonia may complicate all the local- 
izations of diphtheria, but is met most frequently in 
the course of croup, and especially of croup after 
tracheotomy. It is more frequent in the infant under 
four years, and more grave in the adult. When it 
accompanies diphtheritic angina, it is general. y be- 
cause we have to do with a hypertoxic form of the 
disease; the broncho-pneumonia is then early. In 
croup we observe it sometimes from the first days be- 
fore tracheotomy, sometimes two or three days after 
the operation, sometimes later still, when all danger 
seems to be over. 

In the hypertoxic diphtherias, the physical and 
functional signs of the broncho-pneumonia remain com- 
pletely masked, and the pulmonary lesion is only rec- 
ognized at the autopsy. In the other forms of diph- 
theria it is easier to recognize. But it is always 
necessary in children to base a diagnosis rather on 
the general symptoms and functional disorders than 
on the physical signs, which are tardy and obscure. 

In croup, if the broncho-pneumonia comes on 
after tracheotomy, the infant is pale and restless, the 
dyspnoea being very marked and characterized by a 
great frequency of the respiratory movements, with 
beating of the alse nasi. This is apparent when the 
voice is not altogether extinct, when there is no at- 
tack of suffocation, and the stridulous inspiration is 
very little accentuated. The skin is burning hot, the 
temperature very high. Auscultation reveals nothing 



— 93 — 
characteristic. If, however, it is thought desirable to 
practice tracheotomy, the operation is not followed 
by any relief, and the infant dies at the end of a few 
hours. 

When you perform tracheotomy, even though 
the broncho-pneumonia may not have already com- 
plicated the disease, you have still to fear lest the 
lung may be infected secondarily to the operation. 
If the respiration becomes noisy, and rises above 
forty or fifty per minute, if the expectoration becomes 
suppressed, and if the cannula becomes dry, so that 
the air produces in passing through it a peculiar 
whizzing sound, you may be sure of a broncho-pul- 
monary complication. At the same time the wound 
becomes grayish, and soon expectoration is reestab- 
lished, and the cannula gives vent to a puriform 
sanies which blackens it. The temperature, which 
usually falls two or three days after the operation, 
remains about 40 C. The pulse is more than 150 
per minute. Auscultation still gives very doubtful 
results. The blowing cannula-sound masks or modifies 
the pulmonary signs; you may, however, distinguish 
large mucous rales and sometimes a souffle. 

When the broncho- pneumonia is tardy, it comes 
on at a period when the patient seems to be out of 
danger. The later its onset, as a rule, the more favor- 
able the prognosis; it is always, however, a very grave 
complication, and kills nine times out of ten. 

Erysipelas is a very rare complication in diph- 



— 94 — 
theria, apart from croup and tracheotomy. Some- 
times it supervenes after the latter; you will then see 
the red, tumefied borders of the wound so character- 
istic of this complication. The lips of the tracheotomy 
wound then become dry, take on a palish-blue tint, 
and retract; the redness and swelling extend to the 
neck, face, and whole body. The general state now 
becomes worse, the temperature suddenly rises, and 
with the extension of the erysipelas the patient be- 
comes restless, delirious, and irremediably comatose. 

Measles sometimes complicates diphtheria, es- 
pecially in children's hospitals, where it has such op- 
portunities to spread. This exanthem is more likely 
to attend croup, and especially after tracheotomy. 
The invasion of the diphtheria is announced by an 
arrest in the cicatrization of the wound, and by high 
fever. From the first few days a broncho-pneumonia 
is present, which carries off two-thirds of the patients. 

Scarlatina complicates diphtheria much more 
rarely than does measles. I saw it prevail as an epi- 
demic in August, 1889, in a barrack hospital, among 
diphtheritic patients there quarantined, when it proved 
very fatal. The onset is announced by high fever, 
soon followed by the characteristic eruption. 

Whooping-cough is a rare complication of croup. 
The paroxysms do not increase by the attacks of 
suffocation, but broncho-pneumonia soon sets in, 
with all its dangers. 



CLINICAL FORMS. 

We may, with Trousseau, admit three forms of 
diphtheria: the simple or benign, the infectious, and 
the form that is toxic at the start. This division cor- 
responds sufficiently well with clinical observation. 

i. Benign diphtheria generally appears under the 
form of sore throat, but sometimes attacks pri- 
marily the larynx, and we have then croup from 
the start. The disease announces itself by a slight 
fever, prostration, and malaise. When angina is the 
primary manifestation, there will be redness and 
swelling of the tonsils — often of only one. Over the 
swollen tonsils a white exudate forms, well circum- 
scribed, semi-transparent, which rapidly thickens and 
thus constitutes a loosely adherent false membrane. 
Sometimes, instead of forming a patch covering a 
part of the tonsil, the membrane develops by lenticu- 
lar points well separated, resembling herpes of the 
throat. An eruption of herpes on the lips may in- 
crease still more the difficulties of diagnosis. Gland- 
ular enlargement is the rule, but has, perhaps, less 
importance than Trousseau assigned to it. The false 
membrane remains localized to the throat except in 
rare cases, where it gains the larynx and constitutes a 
purely mechanical danger; but the disease remains 
benign, and, if it is possible to avoid asphyxia, re- 
covery is not delayed. 

These benign manifestations of diphtheria are of 



- 96 - 
short duration; recovery follows at the end of six or 
eight days. Albuminuria is generally lacking; par- 
alysis sometimes appears, however, during conva- 
lescence. However slight the disease seems, and 
however inconspicuous the blood-poisoning, these 
benign forms are able to transmit grave diphtheria. 
This is the first argument to advance to those who 
are unwilling to recognize diphtheria in these light 
manifestations. The second argument is furnished 
by bacteriology, which has revealed the presence of 
the bacillus of Loeffler in all its virulence in these 
false membranes, so little inclined to invade the sur- 
rounding parts. 

Furthermore, there exist abortive cases, in which 
the local symptoms are almost imperceptible, amount- 
ing only to a simple redness of the throat; the false 
membrane is insignificant or absent. Nevertheless 
these cases are met with in times of epidemics by the 
side of the malign forms; their origin is the same, and 
they may, in their turn, give rise to malignant diph- 
theria. We must also add that these abortive cases, 
with local manifestations almost nil, may in some 
cases develop general symptoms of extreme gravity. 

2. Infectious diphtheria generally establishes its 
primary focus in the throat; it may, however, first ap- 
pear on other mucous surfaces or even on the skin. The 
general condition may be the same at the onset as in 
the benign form, but as a rule the fever is quite high. 
The aspect is one of extreme depression. The counten- 



— 97 — 
ance has a pale, leaden hue; the mucous membranes 
are cyanosed. The intelligence is intact during the en- 
tire disease, but the general prostration is pronounced. 
What specially characterizes this form is the capital 
importance belonging to the local symptoms: the false 
membrane is essentially invasive; it spreads largely 
over the tonsils, the soft palate and uvula, gains the 
nasal fossae, the larynx, the bronchi, the lips, the con- 
junctivae, the genital organs, and covers the surface of 
blisters, wounds, and spots of impetigo. In the 
gravest cases it takes on a dark-grayish color with 
gangrenous appearance; the odor is fetid; the gland- 
ular swelling is very marked. In the less severe cases, 
there is always generalization of the false membranes, 
but without the gangrenous aspect ; and the adenopathy 
is very moderate. Lastly, in certain cases, the disease 
for several days has the appearance of a benign diph- 
theria well localized; then suddenly it takes on an 
invading course, and spreads in less than twenty-four 
hours to the nasal fossae, the larynx, and the bronchi. 
The albuminuria, more frequent than in the first form, 
is not constant; but the croup and the pulmonary 
complications are here the rule, and constitute all the 
gravity of the infectious form. Death is a frequent 
termination. During convalescence, diphtheritic par- 
alysis frequently supervenes. 

The progress is slow; the disease lasts generally 
from ten to twelve days, sometimes a month; in cer- 
tain exceptional cases the patient continues to cough 



out false membranes for several months (the chronic 
diphtheria of Barthez). 

3. In the toxic form the danger is no longer con- 
fined to the localization of the false membrane and 
its rapid invading tendency; the exudation plays only- 
an insignificant part compared with the profound and 
rapid intoxication of the organism. 

The accidents may assume a fulminant form, 
with intense fever and rapid collapse, the productioa 
of false membranes being variable, but glandular' 
engorgement excessive with infiltration of the neigh- 
boring cellular tissue; the patient in a few hours falls 
into a typhoid state, which terminates in death in the- 
course of twenty-four to seventy-two hours. 

But the disease generally lasts rather longer. 
The false membranes easily spread from the original 
focus in the throat, and take on a gangrenous aspect 
and fetid odor, the underlying mucosa bleeding at 
the least touch. Haemorrhages are the rule— from- 
the nose, mouth, anus, urethra, sometimes even from 
the stomach and bladder. Albuminuria is constant. 
The glands are extremely swollen. The pulse is 
rapid and becomes filiform; the extremities are cold; 
the temperature of the body is below the normal; the 
patient lies in a state of somnolence very like coma. 
Death is certain, and generally occurs before the end 
of the first week. 

Sometimes the evolution of the toxic diphtheria 
is quite insidious; the false membranes are of little 



— 99 — 
extent, have no tendency to invade, and often disap- 
pear at the end of five or six days. But from the 
onset the glandular swelling is enormous, the pulse is 
wretched, the face livid; then as the local symptoms 
improve, the prostration augments, the pulse be- 
comes feebler, the skin cold, and the patient suc- 
cumbs. 

In ambulatory toxic diphtherias the local lesions 
and the fever are without importance; the patient 
keeps up and is able to walk; but the paleness of the 
face and swelling of the neck cause the physician to 
be watchful from the onset. These diphtherias ter- 
minate unexpectedly in sudden death, or they may 
end in an unforeseen manner in the terminal accidents 
of the collapse. 

Forms Differentiated by Bacteriology. — Loeffler's 
bacillus being recognized as the specific agent of 
diphtheria, it was but natural that efforts should be 
made to harmonize the different clinical aspects of 
the disease with the results yielded by bacteriological 
examination of the false membrane; in other words, 
to ascertain if the Loeffler bacillus suffices of itself to 
explain the entire symptomatic tableau of diphtheria, 
or if in some cases there is not warrant for attributing 
a part or the majority of the symptoms to associated 
pathogenic microbes. Grancher has attempted this 
division, and has proposed the name "toxic forms of 
diphtheria" for those cases in which the Loeffler ba- 
cillus is alone operative, as distinguished from the 



"infectious form" in which the clinical picture is 
completely modified by the secondary infections. 

From a symptomatic point of view, we shall see 
that these two forms are quite different from those 
which bear the same name in Trousseau's classifica- 



tion. 



Barbier has attempted to justify the division pro- 
posed by Grancher, and has studied quite specially 
the influence of the streptococcus pyogenes, so often 
noticed in the false membrane, on the course of diph- 
theria. He admits, first, a pure diphtheritic angina 
(toxic angina of Grancher), due to the Loeffler bacil- 
lus and to it alone. These are the principal charac- 
ters: sore throat often nil (this first phase of the dis- 
ease may be latent and pass unperceived); there 
may be no fever, headache, or backache; the child is 
in not quite its usual good spirits, a little cross, and 
this is all; on examining the throat, typical white 
false-membranes, more or less easily lifted in flakes, 
are seen, but the mucosa is almost normal, neither red 
nor swollen; adenopathy absent or scarcely apprecia- 
ble. Propagation to the larynx is frequent, and the 
symptoms of this may be the first to indicate the 
proper diagnosis. The future of these patients, if the 
type remains pure, is equally characteristic. It is in 
them that we witness the bronchial diphtheria, with 
expulsion by the cannula of pseudo-membranous 
casts, which latter often lead to fatal asphyxia. They 
have coryza, but it is diphtheritic in every aspect, with 



closure of the nasal passages and obstructed mucous 
discharge. The false membrane, by hindering the 
entrance of air, determines the respiratory impedi- 
ment or arrest by the nares. The cannula at no time 
gives vent to pus or muco-pus; it is dry. Death re- 
sults from asphyxia pure and simple, or possibly from 
the nervous accidents — syncope, paralysis — or sys- 
temic intoxication. If recovery follows, the patients 
retain an anaemia more or less marked, and remain 
exposed to nervous accidents of paralytic nature 
during convalescence. 

M. Barbier then considers the phenomena which 
belong to the association of the diphtheria bacillus 
with the streptococcus as shown by bacteriologioal 
examination. In these cases the streptococcus has 
been found, not only in the throat, but also in the 
viscera and in the blood, and all the complications 
were either certainly or probably of streptococcus ori- 
gin. The following description shows how this micro- 
bian association manifests itself clinically, giving rise 
to the streptococcus form of diphtheria, one of the 
varieties of the "infectious form" of Grancher: 
"Typical external aspect of face and neck: Face pale, 
swollen or cyanosed, leaden hue; skin shiny and 
sometimes rosy red around the nose and on the nose 
itself; redness and excoriation of the upper lip beneath 
the nostrils; mouth open, breath horribly fetid when 
the bacteria of putrefaction have invaded the exu- 
dates, which is not rare; the act of swallowing is very 



painful; the patient refuses nourishment; throat much 
tumefied, the mucous membrane red, sanious, bleeding, 
swollen; false membranes often dissociated and absent, 
or even thick and flabby, putrilaginous; neck enor- 
mously swollen, owing to the tumefaction of the glands, 
which are, as it were, buried in an cedematous infiltra- 
tion of the cellular tissue of the neck; abundant nasal 
discharge, sero-fibrinous, sero-sanguineous, color of 
tobacco-juice, or even completely hemorrhagic— so 
great is the abundance that sometimes the liquid flows 
by drops. The disease often kills in the course of 
twenty-four hours; if the patient lives longer, compli- 
cations due to the streptococcus appear. The pros- 
tration of the patient, or oftener the extreme agita- 
tion, the high fever, sometimes convulsions at the end, 
are the principal general phenomena observed. Re- 
covery is rare in the infectious forms; convalesencc 
protracted. The throat, nose, and the outer border of 
the nose, long remain red and excoriated; grayish 
ulcerations, locally painful, are seen in the throat, and 
in certain cases actual losses of substance affecting the 
pillars of the fauces and the soft palate occur. Later 
complications, such as suppurative adenites, phleg- 
mons, etc., may still retard the recovery and even 
produce death." 

This attempt at classification of the clinical forms 
of diphtheria is interesting, though necessarily incom- 
plete, and it indicates well the way to take in order to 
complete our knowledge of the characters so varied 



— 103 — 
-and so dissimilar which diphtheria may present. 
There remains still to be studied the action on the 
economy of the micro-organisms of the false mem- 
branes other than the streptococcus, and to group 
together a great number of facts well studied in 
order to fix definitely these different aspects which 
the microbian associations impress upon diphtheria. 
Quite recently, Martin has reported cases which seem 
to show that the bacillus of diphtheria, associated 
with a coccus which often appears as a diplococcus 
capable of forming abundant colonies on serum, which 
bear a marked resemblance to those of the Loeffler 
bacillus, gives rise to a quite benign form of diphthe- 
ritic angina; while the association of the staphylococ- 
cus albus with the specific bacillus implies a prognosis 
much more grave. 



DIPHTHERIA IN ADULTS. 

Diphtheria is quite rare in adults; when it does 
occur, it is generally more grave than in children. 
Very benign epidemics among adults have, however, 
been reported. And in cases where the toxine of 
diphtheria spares the patient, respiratory complica- 
tions of a grave, often fatal, character, are liable to 
supervene. The aspect of croup in the adult is dif- 
ferent from what it is in the child; the glottis being 
large, the false membranes very seldom become suf- 
ficiently developed to completely occlude it and pre- 
vent the entrance of air. Moreover, the false mem- 
branes hardly ever remain limited to the laryngeal 
cavity; the laryngitis is accompanied by pseudo- 
membranous tracheo-bronchitis. 

Croup in the adult has a progressive course; it 
does not pass through the three very distinct periods 
observed in this disease in children. The voice, 
which almost always escapes complete extinction, 
may remain normal till death, although the vocal 
cords are covered with false membranes. The dysp- 
noea is progressive, without attacks of intercurrent 
suffocation. Death by progressive asphyxia is the 
rule; it comes on tardily, on the average at the end 
of two or three weeks. The concomitant manifesta- 
tions along the entire bronchial tree easily explain 
why tracheotomy is of so little relief to the adult. At 
the same time this operation should not be neglected 



— i°5 — 
in cases of threatened asphyxia, for instances of cure 
due to tracheotomy are on record. 

Very often in the adult, diphtheria takes the 
hypertoxic form. The patients are overwhelmed 
from the onset. The extremities are cold; the pulse 
small, irregular; the face pale, of a leaden hue; the 
breath fetid. A yellowish serosity flows by the nasal 
fossse, of sickening odor. The patients are also 
enfeebled by an incessant diarrhoea. The throat is 
lined with thick, putrilaginous false-membranes, and 
when these are removed a bleeding surface is left 
behind. The blood mixes with the exudate and colors 
it; the mucous membrane itself takes on a darkish 
hue, as if gangrenous. The submaxillary glands are 
very much engorged and painful, the surrounding 
cellular tissue infiltrated, and the entire neck tumefied. 
If the air-passages are invaded, the symptoms of 
croup are scarcely apparent; the dyspnoea and the 
cough are so little marked as hardly to attract atten- 
tion to the larynx. The patients die of the blood- 
poisoning rather than by asphyxia. 

We know with certainty that the form of puer- 
peral infection called diphtheritic, accompanied by 
false membranes on the vulva and vagina, is not due 
to the Loefner bacillus. True diphtheria is very rare 
during pregnancy. 



SECONDARY DIPHTHERIAS. 

When diphtheria supervenes in the course of an- 
other disease, it generally takes on a very marked 
character of malignancy, and localizes itself especially 
on the organs which are attacked by the primary dis- 
ease. Its course is rapid, especially when it leads to 
death. Diphtheria may complicate all diseases: 
tuberculosis, typhoid fever, pneumonia, etc. It is less 
often a complication of scarlet fever than has been 
supposed. It very exceptionally attends the onset of 
scarlatina, for the pseudo-membranous angina of this 
period is seldom of diphtheritic nature. On the other 
hand, the pseudomembranous anginas which super- 
vene at a late period (the second week) are almost 
always manifestations, of diphtheria; the scarlatina, 
after a normal course of a few days, has disappeared 
as well as the initial angina, the temperature has 
fallen to the normal, desquamation has already set in, 
when unexpectedly the general condition becomes 
aggravated, the child grows pale, the fever kindles 
up, and the glands of the neck become engorged. 
On examining the throat, we find it filled with grayish 
false-membranes. Patients affected with these late 
anginas generally succumb rapidly with all the symp- 
toms of diphtheritic poisoning. 

Diphtheria following measles is also of extreme 
gravity. Under two years, death is almost certain; 
patients die of infection or of broncho-pneumonia. 



— 107 — 

Diphtheria is very rarely a complication of 
whooping-cough, appearing chiefly during the spas- 
modic period. The paroxysms of coughing may then 
act favorably in aiding the expulsion of the false 
membranes. According to Vaquer, the toxic form is 
rarely observed, but broncho-pneumonia is always to 
be dreaded. It will not do to hesitate to practice 
tracheotomy when indicated, for this operation has 
saved a number of lives. 

Diphtheria secondary to typhoid fever and small- 
pox terminates fatally in a few days. As a complica- 
tion of typhoid fever it rarely assumes a form other 
than the hypertoxic. 



PROGRESS— DURATION— TERMINATION. 

When studying the clinical forms of diphtheria, 
we saw that this disease was complex, and that it 
would be impossible to include a satisfactory account 
of its course in one description. 

In one case, for example, diphtheria appears in a 
benign form, remains local and circumscribed, occa- 
sions a little fever for a few days; the false mem- 
branes hardly re-form, soon disappear, leaving a little 
redness of the mucosa. All the symptoms disap- 
pear in about a week; the patient, however, remains 
for some time pale and feeble, and has a slow conva- 
lescence. 

Again, the production of the false membrane is 
exuberant and becomes a real danger. It spreads 
rapidly, invades new surfaces, and when removed is 
reproduced; the general condition is not bad, but the 
exudation may at any moment obstruct the air- 
passages, and then asphyxia is imminent. This form 
sometimes lasts a fortnight, sometimes a month. 

Take another case: The patient is unconscious, 
his countenance livid, neck and face much swollen, 
respiration panting and becoming extinct. Profound 
systemic intoxication is present. It often requires an 
attentive examination to find the false membrane 
which is the origin of all the evil. In the course of 
five or six days, sometimes in twenty-four hours, the 
diphtheria has invaded the entire organism. 

By these examples it is apparent how variable is 



— 109 — 

the course of the disease. At the same time, when 
the false membrane does not remain absolutely local- 
ized at the point of primary infection, the process of 
invasion follows a sufficiently regular course: you see 
the membrane spread to the throat, nasal fossae, 
larynx, trachea, bronchi, etc. If the law of Breton- 
neau and of Trousseau, thus formulated: "The 
propagation takes place in an invariable order from 
the upper parts to the lower " — if this law is not 
absolute, it nevertheless indicates how completely 
these two observers had recognized a sort of auto- 
inoculation, of successive contamination of the parts 
below by a liquid secreted by the false membrane 
above. Evidently the contagion may spread upward 
as well as downward, as in cases where it passes from 
the pharynx to the Eustachian tube, and from the 
nose into the nasal duct; but we must not forget that 
there are also instances where the contagion is carried 
by the fingers of the patient or those of his attendant. 
But these facts are not sufficient to invalidate the law 
of Bretonneau, which finds justification in practice. 
Diphtheria usually runs its course in from two or three 
days to a month. There are exceptional cases where 
the diphtheria becomes chronic and the patient con- 
tinues to expel false membranes after two or three 
months. 

Death is the termination of diphtheria in more 
than two-thirds of the cases; it may supervene sud- 
denly during the first two or three days of the disease. 



Sometimes it terminates the hypertoxic anginas with 
fulminant development, the patient succumbing to a 
veritable hyperacute septicaemia. Then again, in diph- 
theria which has early invaded the air-passages, in a few 
days menacing asphyxiating symptoms appear; this 
is the strangulator)' diphtheria, against which trache- 
otomy remains powerless if there be pseudo-membra- 
nous bronchitis, or if the diphtheria be complicated 
with broncho-pneumonia. Sometimes the patient suc- 
cumbs to the early cardiac paralysis first mentioned 
by Henoch. 

During the stationary period (fastigium), croup 
and broncho-pneumonia are ^likely to carry off the 
patient more or less rapidly. When there are no 
diphtheritic manifestations in the air-passages, the 
disease may terminate slowly by a progressive ca- 
chexia, due either to the nature of the intoxication or 
to the disorders produced by secondary infections, 
such as gangrene, phlegmons of the neck and groin, 
mediastinitis, erysipelas, or an intercurrent eruptive 
fever. 

Even in convalescence, all danger is not past; an 
acute myocarditis, passing from latency to activity, 
may cause sudden death. Rapid asphyxia is always 
imminent when the respiratory muscles become para- 
lyzed; this frequently happens as a sequel in diph- 
theritic paralysis. Sudden syncope follows a crisis of 
.bulbar or cardiac paralysis. In full convalescence, 
broncho-pneumonia may attack a patient and carry 
him off. 



Recovery very often follows the simple forms 
of diphtheria. Unfortunately these are far from 
being most frequent. Not all patients succumb to 
those invasive diphtherias which constitute the " in- 
fectious form " of Trousseau; some of them will re- 
sist croup, tracheotomy, broncho-pneumonia, the 
paralysis of convalescence. But the toxic or hyper- 
toxic form is always fatal. 

Recovery is announced by the progressive dis- 
appearance of the false membranes, which reappear 
more and more slowly; the adenopathies diminish, 
the general state improves, and after a convalescence 
always rather slow, complete restoration comes about. 

A first attack confers no immunity from future 
attacks; the patient is subject to relapses and recur- 
rences. It is not rare to see the false membranes re- 
appear several days after the advent of convalescence. 
There is nothing surprising about this, for we know 
that the bacillus with all its virulence lives in the 
mouth for some time after the false membranes have 
completely disappeared. I have seen croup follow 
recovery from a benign diphtheritic angina. Often 
the second attack of diphtheria is more benign than 
the first, but there are numerous exceptions to this 
rule. 

Relapses may be occasioned by eruptive fevers, 
such as measles or scarlet fever. Single recurrences 
of diphtheria have been frequently noted, and in some 
cases even multiple recurrences. 



PROGNOSIS. 

When the false membrane remains localized and 
shows little tendency to spread and to be reproduced, 
the air-passages remaining free and the neighboring 
glands being little affected, the general state good, 
and little or no albuminuria, there is reason to regard 
the disease as benign and to hope for a favorable 
termination. But the diphtheria none the less re- 
mains a grave disease, for even in these cases, so 
\ght in appearance, there is always danger of late 
croup, a myocarditis, or a paralysis during conva- 
lescence. 

Diphtheria comprehends three factors of gravity: 
the patient, the disease, and the environment. 

Diphtheria is particularly grave in the infant and 
in the adult. Before the third year of life it is almost 
always fatal. 

The previous health of the patient is also a mat- 
ter of importance. Lymphatic or scrofulous subjects 
appear to present a favorable soil for grave infec- 
tions. The malignancy of secondary diphtherias we 
have already discussed. 

The course of the disease may be influenced in a 
capital manner by the degree of localization of the 
diphtheritic infection, by the extent of systemic in- 
toxication, and by the nature of the infectious com- 
plications. 

The rapid extension of the false membranes to 



— H3 — 
the nasal fossse, the larynx, and the bronchi, is of 
special gravity by reason of the mechanical troubles 
it occasions. As for the pseudo-membranous coryza, 
it is always of bad prognosis, for it indicates the in- 
tensity of the infection. Often the quite special viru- 
lence of the bacillus is already announced locally by 
the putrilaginous, sometimes gangrenous, appearance 
of the false membranes. 

The poison soon makes its action felt on the en- 
tire organism. The glandular engorgement, the pallor 
of the visage, the prostration, the haemorrhages of 
the first few days, especially that constant oozing 
from the mouth and throat which we so much dread 
to see, are precious elements of prognosis; the fever 
and albuminuria are much less important. 

But the intoxication may be slow and insidious, 
suddenly manifesting itself in convalescence by a 
myocarditis or paralysis. It is at the advent of con- 
valescence that it is necessary particularly to watch 
the heart, whose most profound lesions announce 
themselves only by troubles trifling in appearance — a 
little precordial distress, palpitations, lipothymia. 
Likewise, a paralysis which begins by an insignificant 
difficulty of deglutition may become rapidly general 
and carry off the patient in a few days. 

Secondary infections may determine veritable 
septicaemias, at the same time that they aggravate the 
virulence of the diphtheria bacillus; the extreme 
pallor of the countenance, the deformation of the in- 



— ii 4 — 

filtrated neck, the yellowish, sanious and fetid dis- 
charge from the nares, the agitation or the somno- 
lence, the general enfeeblement, leave no doubt as to 
the issue of the disease. 

The gangrene which may complicate the diph- 
theria testifies less to the dilapidation of the patient's 
organism than to the gravity of the disease itself. It 
is nevertheless of serious prognosis. 

There is general agreement that the infectious 
erythemata which supervene at the onset of diph- 
theria have no influence on the course of the disease. 
It is not so with the late erythematous rashes, which 
are almost always precursors of death. 

Broncho-pneumonia is one of the most grave 
complications of diphtheria. We have seen how little 
we can depend upon the physical signs in making a 
diagnosis. It is chiefly the coincidence of a very high 
elevation of temperature with a marked and growing 
dyspnoea that will help the practitioner to recognize 
this affection, which is so very fatal. 

Bad hygienic conditions, close, ill ventilated 
rooms, overcrowding, want of cleanliness or of nour- 
ishment, are unfavorable circumstances. 

The danger is of course greater in certain epi- 
demics of peculiar malignancy; diphtheria is also espe- 
cially fatal in large cities. It is generally very malig- 
nant in winter and in the spring time, in cold and 
damp seasons, and in certain northern countries such 
as Sweden, Norway, Denmark, and Northern Ger- 
many. 



DIAGNOSIS. 

The elements which contribute to the diagnosis 
of diphtheria are not all of equal importance. The 
principal one, undoubtedly, is the false membrane — a 
fibrinous exudation, of whitish or grayish color, quite 
adherent to the parts beneath, forming when removed 
a coherent lamina insoluble in water, and reproduced 
in the throat after ablation. Angina being the most 
frequent manifestation of diphtheria, the presence of 
a pseudo-membranous exudation on the tonsils is 
very significant, especially when it spreads to the soft 
palate and the uvula. 

The engorgement of the glands corresponding to 
the region invaded by the false membrane, the pallor, 
the general enfeeblement of the patient, the albumin- 
uria, may also give valuable indications. The paraly- 
sis during convalescence, even, by its special behavior 
and evolution, is enough sometimes to warrant a retro- 
spective diagnosis when every other manifestation of 
the diphtheria has d ; sappeared. 

But these characteristic symptoms are not always 
very apparent. In very young children, particularly, 
the disease is frequently overlooked by reason of 
inattention to the throat. Trousseau with good rea- 
son advises to examine the throat in every case of ill- 
defined infantile sickness. 

Every one of the elements of diagnosis above 
mentioned may be wanting. Anginas without false 



— n6 — 

membranes have been observed in the course of cer- 
tain epidemics. They alternate with the ps udo 
membranous manifestations, are contracted by con- 
tact with an undoubted case of diphtheria, and trans- 
mit an angina with characteristic exudation. But 
these "diphtherias without diphtheria" tre too excep- 
tional to occupy us long. On the other hand, it is not 
rare to see the false membrane appear discrete and 
become detached in a day's time or less, and not 
again be reproduced; nor need the ephemeral nature 
of the characteristic local symptoms have any influ- 
ence on the evolution of the disease. In other cases, 
and especially in he benign forms, the glandular en- 
gorgement is wanting; the general condition may 
remain good; the albuminuria may be absent. An 
eruption of herpes on the lips or nares is not a symp- 
tom of much significance, for it may coincide with 
genuine diphtheria as well as with herpetic angina. 

The diagnosis of acute diphtheritic myocarditis 
is very difficult. In the young child who in full con- 
valescence is suddenly carried off by a syncope, the 
cause of the terminal accident is very difficult to de- 
termine and to distinguish from a cardiac paralysis, if 
the medical attendant has not previously noted an 
extreme feebleness of the pulse accompanied by 
cardiac intermittences. In the adult the symptoms 
evolve less rapidly; first a praecordial anguish, then 
cardiac excitation, soon followed by feebleness of the 
organ with irregularity and softness of the pulse, 



— ii 7 — 
dyspnoea, collapse, and repeated syncope. Unhappily, 
these symptoms may accompany pleuro-pneumonia 
or pericardiac complications, which must first be 
eliminated by an attentive examination before the 
physician can decide that he has an acute myocarditis 
to deal with. 

The diphtheritic paralysis is generally easy to 
recognize, especially when account has been taken of 
the manifestations of diphtheria which have preceded 
it. In the exceptional cases, where the paralysis re- 
mains localized to the lower members without having 
ever affected any other part, it is distinguished from 
certain peripheral neuritic paralyses, and particu- 
larly from alcoholic paraplegia, by the absence of pain 
and especially of muscular atrophy. If it sometimes 
has a superficial resemblance to general paralysis, 
glosso-labio-laryngeal paralysis, multilocular sclerosis, 
or locomotor ataxia, it is sufficient to bear in mind its 
history and peculiar signs in order to avoid any 
confusion. 

We have already seen of how little help are the 
physical signs in enabling one to decide as to the in- 
vasion of broncho-pneumonia in the course of diph- 
theria. A high fever, a marked and continuous dysp- 
noea, with beating of the alse nasi, even when there 
are little or no paroxysms of suffocation or of wheez- 
ing, are symptoms quite as precious as those furnished 
by auscultation and percussion. 

Thrush rarely resembles diphtheria. It may, 



however, extend to the throat, and even localize itself 
there exclusively, so as to cause doubt in the mind 
of the attending physician. The constitution of its 
grumous coating should dissipate these doubts. 
Moreover, if you take a little of the thrush membrane, 
crush it on a glass slide, and treat it with potassa, you 
will see under the microscope the mycelium and 
spores of Oidium albicans. 

When diphtheria passes from the throat to the 
larynx, one is warned of the laryngeal nature of the 
lesion by noting the patches in the throat. But in 
cases of primitive croup or where the patches in the 
throat have disappeared, the diphtheria reveals itself 
only by the mechanical obstacle which it opposes to 
the respiratory functions. Now in the infant the 
affections which cause similar symptoms are numer- 
ous, by reason of the small diameter of the glottis. 
There is only one sign pathognomonic of diphtheria 
exclusively localized in the larynx, namely, the ex- 
pectoration of a false membrane, and this is often 
wanting. 

In laryngismus stridulus, the first access of suffo- 
cation comes on suddenly in the night; the patient 
may have had only a little cold in the head or a little 
hoarseness during the day, perhaps no abnormal symp- 
toms whatever. In the interval of the paroxysms the 
voice is rarely altered, and the cough is resonant, the 
respiration calm; while in croup the voice and the 
cough are rapidly and completely extinguished, the 



— II 9 — 

•dyspnoea becoming more intense as the paroxysms 
are repeated, and never presenting complete remis- 
sion. 

Retro-pharyngeal abscess or oedema of the glot- 
tis may also narrow the glottic orifice so as to give rise 
to symptoms of asphyxia very like those of croup. It 
will not do to neglect exploration of the pharynx and 
upper part of the larynx with the finger introduced 
into the throat, before pronouncing on the nature of 
the disease. 

The differentiation of the false diphtherias will 
be considered on the next page. 



FALSE DIPHTHERIAS. 

The affections just enumerated resemble diph- 
theria more or less, but it is almost always possible to 
differentiate them objectively. It is not so with the 
diseases we are about to study; they reproduce com- 
pletely the clinical picture of diphtheria, and differ only 
by their course and prognosis. Often a bacteriological 
examination is absolutely necessary, to remove doubts. 
In a scarlatinous patient who in the first two or three 
days of the disease has had an erythematous angina, 
possibly accompanied by a pultaceous deposit, the 
aspect of the throat will be modified on the second or 
third day of the eruption, and thick lenticular points 
are visible at the orifice of the tonsillar crypts; these 
points soon run together and form a creamy coat 
with a pultaceous aspect, but with little power of 
resistance. The next day there is a firm, coherent 
false-membrane, which may be removed in large 
flakes. This pseudo-membrane invades the uvula 
and soft palate, and may spread to the pharynx. 
Very white at first, it soon becomes grayish or yel- 
lowish; may be strewn with black patches, the result 
of little haemorrhages. The pseudo-membranous de- 
posit is very adherent to the mucosa, and reproduces 
itself after ablation. Often, when it is removed, the 
mucous membrane underneath bleeds and shows an 
eroded, ragged, sloughy, indented surface. The dys- 
phagia and sniffling are pronounced. There is accom- 



panying this bad condition of the throat, engorgement 
of the submaxillary glands. The temperature is high. 
According to the degree of extension of the false 
membranes, the gravity of the general symptoms, and 
the amount of general infection attributable to the 
angina, we may distinguish three forms of this sore 
throat: In the benign form the false membranes are 
very limited and have but little tendency to spread; 
the neighboring glands are only slightly swollen; the 
general condition is good, and the fever lasts but a 
short time; no complication sets in as a consequence 
of the angina; the false membranes may early invade 
the tonsils and uvula, tut have little tendency to 
re-form, and rapidly disappear; the angina causes no 
general symptoms. — The grave form is characterized 
not only by the rapid extension of the false mem- 
branes, by their persistence, and by the intensity of 
the submaxillary engorgement, but also by the long 
duration of the angina, which, in the cases which I 
have observed, has lasted from nine to twenty-three 
days; the fever and general symptoms are prolonged, 
and there are almost always complications, such as 
broncho-pneumonia, nephritis, rheumatism, otitis, im- 
petigo, etc.; this form does not of itself cause death, 
but it makes the prognosis doubtful by the com- 
plications which it entails. — If in the forms before 
mentioned, the symptoms independent of the angina 
are the most noteworthy, it is not so in the scarlatinal 
septic form; an atypical, fugacious eruption, scarcely 



visible, characterizes this variety; the other symptoms 
depend only on the angina, which seems of itself to 
constitute the whole malady, hence the name of scar- 
latina anginosa which is often given it. The most 
complete descriptions of hypertoxic diphtheritic an- 
gina give a faithful portraiture of the septic angina of 
scarlet fever. 

I have proved the existence of these different 
forms by numerous bacteriological examinations. By 
the process of sowing in striae on gelatinized serum 
and gelose, I have made bacteriological examination 
of nineteen cases of pseudo-membranous angina at 
the onset of scarlatina. Only one of these anginas 
was of diphtheritic nature; in the eighteen other cases 
not a single colony of the Loeffler bacillus could be 
found, but the presence of the streptococcus pyogenes 
was constant in the false membrane. 

It is to-day settled that pseudo-membranous 
angina at the onset of scarlet fever is almost never 
of diphtheritic nature; this affirmation is based on 
forty-five cases in which bacteriological examination 
was made with all the rigor possible. On the other 
hand, the pseudo-membranous angina which comes 
on at a late date in scarlet fever is almost always true 
diphtheria. In five out of six cases examined by 
Loeffler, Morel, and myself, the Loeffler bacillus was 
found, the sixth case being a streptococcus diphtheria, 
in which the patches did not appear till the twenty- 
seventh day, during convalescence. 



We know there is a form of puerperal infection 
improperly denominated " puerperal diphtheria," in 
which true fibrinous false-membranes are found on 
the vulva, vagina, mucosa of the uterus and tubes, 
and even on the serous membranes. Suppurations 
are often among the symptoms. This fibrinous exu- 
dation presents characters very similar to those of 
diphtheritic membranes; but M. Widal has sufficiently 
differentiated them by showing that while the patches 
of diphtheria are due to the Loeffler bacillus, those of 
puerperal infection are the product of the strepto- 
coccus pyogenes. 

It is not rare to note in syphilitic patients, some- 
times on the surface of an infectant chancre, oftener 
on secondary syphilides, a thick, grayish, adherent 
false-membrane very like the diphtheritic exudate. 
When it forms only a simple grayish film, we have the 
opaline papule; when thicker, lamelliform, opaque, of 
a dull white color, it is the porcelain-papule of Four- 
nier. It is in general on the genital organs of the 
female that we observe syphilitic lesions thus covered 
with false membranes; they may also be met in the 
throat, and strikingly resemble diphtheritic angina, 
for which they have been frequently mistaken. The 
onset of these diphtheroid anginas of syphilis is ac- 
companied with engorgement of the submaxillary 
glands and with general symptoms often very marked: 
malaise, chills, cephalalgia, fever, pale and earthy hue 
of countenance. 



— I2 4 — 

The clinical signs which enable us to differentiate 
the pseudo-membranous syphilides from diphtheria 
are not constant. The objective characters of the 
false membranes are the same in both affections. At 
the same time, in most cases the diphtheritic patch 
may readily be detached with a swab, while the 
syphilitic exudate resists a mere rub. The subjacent 
mucosa is almost always intact in diphtheria; whereas 
it bleeds easily and almost always presents ulcerations 
when the false membrane is syphilitic. When true 
diphtheria spreads, it easily reaches the posterior 
pharynx and trachea; the diphtheroid syphilide gen- 
erally respects the larynx, and does not spread be- 
yond the anterior pillars of the soft palate. In 
syphilis, false membranes may be present on the hard 
palate, while this localization is exceptional in diph- 
theria. The pallor, the general prostration, the pres- 
ence of albumen in the urine, are symptoms which 
pertain rather to diphtheria than to syphilis. The 
recognition of syphilitic antecedents, and especially 
the detection of concomitant secondary syphilides, 
plead in favor of syphilis. So much for the differ- 
ential diagnosis of these two pseudo-membranous 
affections. 

Roux and Yersin have noted several cases of 
primary pseudo-membranous angina which were not 
of diphtheritic nature. Menetrier reports a case in 
which he isolated the pneumococcus. Netter has 
also noticed the presence of the pneumococcus in 



— i25 — 
laryngeal false-membranes- when there was no Loef- 
fler bacillus present. In two cases which I personally- 
studied in 1890, and which were tabulated as false 
diphtheria, both occurring in our hospitals, the pseudo- 
membranes did not contain the LoefHer bacillus, but 
gave fine cultures of the streptococcus pyogenes. Net- 
ter has also noted a case of diphtheroid angina due 
to streptococci and staphylococci. Baginsky, out of 
ninety-three cases of apparent diphtheria, found 
sixty-eight due to the Loeffler bacillus, and fifteen to 
staphylococci and streptococci. Examples of these 
false diphtherias have been given by Morel, Mussy, 
and Martin. 

If most of these cases behave clinically like be- 
nign diphtheria, sometimes these false diphtherias are 
accompanied by grave general symptoms, such as 
infectious erythema, and great engorgement of the 
glands, and end in death. 



PATHOLOGICAL ANATOMY. 

We have to study successively the lesions pro- 
voked by the diphtheritic bacillus, those which are 
due to the action of the toxine produced by the bacil- 
lus, and those which result irom the secondary infec- 
tions supervening in the course of the diphtheria. 

i. Lesions Due to the Diphtheria Bacillus.— 
We have seen that the diphtheria bacillus produces 
but one lesion, the false membrane. We have already 
studied the physical characters and the various local- 
izations of the false membranes in the regions acces- 
sible to view. When at the autopsy we inspect the 
false membranes which have invaded the air-passages 
— larynx, trachea, and bronchi — we see that they 
have taken the form of these organs; they line them 
continuously or in patches. We meet them princi- 
pally at the base of the epiglottis, on the aryteno- 
epiglottidean ligaments, on the upper surface of the 
vocal cords, etc. In the trachea, they line chiefly the 
posterior wall. They may also be found in the 
sinuses of the face, the Eustachian tube, and the 
middle ear, to the walls of which they are moulded. 
It is very rare to observe them in the digestive tube. 
In the oesophagus they become elongated into bands 
lining the organ to some depth, or into cylinders more 
or less elongated. In the stomach they form very 
thin patches or rings around the cardia or pylorus. 
In the intestine they spread out in patches or form 
cylindrical moulds of the gut. 



— I2 7 — 

From a chemical point of view, a false membrane 
is composed of the following elements: fibrin, an 
amorphous substance, mucin, and fatty matters. A 
more interesting study because of its practical con- 
sequences is that of the action of chemical agents on 
the exudation. Very few acids have more than a 
slight action upon it; the mineral acids and acetic 
acid cannot dissolve it; it is, however, soluble in 
citric and especially in lactic acid. False membrane 
left in a 5-per-cent. solution of lactic acid dissolves in 
a few minutes. The same result takes place with the 
alkalies, potassa, soda, and lime. Lime-water has as 
rapid an action as lactic acid; and we may obtain 
still better results with a solution of caustic soda in 
glycerin. 

Bretonnean was the first to establish the fibrinous 
nature of the false membrane, and to show that it is 
not constituted by an eschar of the subjacent mucosa. 
Since then, pathologists have explained the formation 
and constitution of the diphtheritic membrane in two 
ways: some hold that it is a fibrinous exudation, 
others that it is a special transformation of the epithe- 
lium of the mucosa. 

The first view is supported by the French school 
— by Bretonneau, Trousseau, Laboulbene, Robin — 
who regard the pseudo- membrane as an exudation of 
fibrin which in its coagulation imprisons epithelial 
elements, fatty matters, and various products of in- 
flammation. The second theory is that of the Ger- 



128 

man school, first stated by Virchow, and subsequently 
developed by Wagner. The latter describes the 
formation of the false membranes in the pharynx by 
a process beginning with the development of a clear, 
homogeneous reticulum, the meshes of which contain 
lymphoid cells; this reticulum being directly derived 
from a particular metamorphosis of the pavement 
epithelia. The latter swell; little, clear, round-oval 
spaces develop around the nucleus, and increase in 
size while deforming the cell. At the same time the 
protoplasm resists further destructive agencies, and 
resembles fibrin by its chemical composition, while its 
nucleus disappears. The deformation of the cellu- 
lar protoplasm becomes more and more marked; it 
elongates and forms filaments, which ramify in every 
direction, and, joining those which issue from neigh- 
boring cells, form with them a continuous network. 
The most superficial cells of the epithelial layer do 
not participate in these alterations. Below the glottis 
and in the trachea the exudation has still an epithelial 
origin, but as the epithelium is cylindrical the reticu- 
lum is closer. Wagner admits that this transforma- 
tion of the cylindrical cells is much more difficult to 
see. 

According to Leloir, we are to seek for a true 
conception in a sort of eclecticism — the epithelial 
alteration constituting, as he believes, a stage of 
onset, the fibrinous exudation corresponding to a 
more advanced stage. During the catarrhal period 



— i2 9 — 
of the diphtheritic angina, when there is still only red- 
ness of the tonsils, the epithelium swells, then its cells 
are glued together, and the false membrane is formed 
at the expense of a transformation and deformation 
of the epithelium different from that described by- 
Wagner, but ending in the same result, an epithelial 
reticulum. Thus there is formed a network con- 
taining in its meshes leucocytes and fibrin in a fila- 
mentous state. If the duration of the false membrane 
is ephemeral, and if recovery is rapid, the process is 
arrested here; there is a complete disintegration of 
the exudation, which disappears, and a new epithe- 
lium is formed on the surface of the mucosa. If the 
disease continues, the epithelial reticulum undergoes 
disintegration, and to replace it the derm throws out 
fibrin and leucocytes which coagulate into a fibrino- 
purulent membrane. Little by little the metamor- 
phosis goes on until there remain in the false mem- 
brane only a few granulo-fatty epithelial cells, and it 
is constituted throughout its extent by a fibrinous net- 
work containing leucocytes and a few red blood- 
corpuscles. 

In the laryngo-bronchial false-membranes, vacu- 
oles indeed form in the disaggregated epithelial cells, 
but there develops rapidly a fibrinous exudate which 
sometimes traverses the dissociated epithelium to 
constitute on its surface a more or less thickened 
muco-purulent fibrinous false-membrane; sometimes 
it raises the epithelium and forms under it a fibrino- 
purulent layer. 



— i3° — 

Leloir shows that there is no difference, macro- 
scopic or microscopic, between the false membrane of 
diphtheria and that which is produced by experiment- 
ally irritating the pharyngeal mucosa, or which de- 
velops in herpetic angina, on mucous patches, indu- 
rated chancres, blisters, etc. In fact, the false mem- 
brane is only a pustule or a mass of confluent pus- 
tules, of which the centre is bare by reason of the 
absence of the horny layer. 

Cornil has also studied the false membrane in 
diphtheria. He admits that the exudate is formed at 
first of a stroma of epithelial cells and leucocytes, 
then becomes entirely fibrinous. There is first a de- 
generation of the investing epithelium; then this is 
lifted up and detached by the migratory cells, which, 
by reason of the inflammation, issue in great abund- 
ance from the vessels of the mucosa. Later, when 
this epithelium is destroyed and does not form again,, 
the false membrane is constituted only of a reticulum 
of fibrin and of leucocytes. 

To sum up: It is admitted that the false mem- 
brane, wherever located, is always essentially the same. 
The importance of the epithelium in the formation 
has been much exaggerated; we indeed find pavement 
epithelium, especially at the outset, in the pharyngeal 
exudate, but fibrin is the principal element of the false 
membrane. 

The Loeffler bacillus in contact with a mucous 
membrane produces an inflammation, which manifests 



itself by the transudation of fibrin through the vessels, 
and by diapedesis of leucocytes. While the false 
membranes experimentally produced — by means of 
ammonia, for instance — are not, after removal, repro- 
duced in the throat, the exudate of diphtheria is 
renewed as long as the cause that has produced it 
(the specific bacillus) remains present and preserves 
its virulence. These successive exudations may give 
a stratified aspect to the false membrane. 

The false membrane may disappear in two ways: 
either it undergoes disaggregation, or it falls off. In 
the first case the fibrin loses its fibrillary character, be- 
comes granular, may be transformed into mucin, soft- 
ens, becomes diffluent, separates in fragments, and 
disappears. This process is accompanied by a notable 
diminution or even complete disappearance of the 
specific bacilli in the exudate, which is invaded by a 
host of other microbes; these bacteria probably con- 
tribute thus to alter the constitution of the false mem- 
brane. 

The pseudo-membrane may become detached 
from the mucosa when the inflammation diminishes 
and the diapedesis and transudation of fibrin cease. 
The mucosa, on becoming normal, secretes mucus, 
which, insinuating itself between the surface of the 
mucosa and the exudate, breaks the filamentous adhe- 
sions which join the two, and detaches little by little 
the false membrane, allowing it to fall off. 

2. Lesions Produced by the Diphtheritic 



Poison. — Bretonneau, in endeavoring to demonstrate 
that the false membrane is not an eschar, affirmed 
the absolute integrity of the subjacent mucosa in all 
cases. He went too far; the mucosa is not unaffected. 
In the most simple cases it is congested but remains 
smooth; at other times, the inflammation being more 
intense, the mucosa becomes rough and loses its 
polish. Below the false membrane and in the zone 
that surrounds it, the chorion is infiltrated to such an 
extent as sometimes to give rise to oedema of the 
glottis; the mucosa is spotted with ecchymoses. 
Often, then, the region invaded is the seat of ulcer- 
ations more or less deep. Lastly, in certain malig- 
nant forms the mucosa takes on a violaceous tint, the 
diseased points become the seat of a considerable 
tumefaction, and a more or less extensive eschar 
forms which leaves after it a grayish ulceration 
secreting a fetid sanies. Roux and Yersin, in cases 
of experimental diphtheria (with the Loeffler bacillus 
alone), have observed destructive lesions of the 
affected region; these eschars at the point of inocu- 
lation have been reproduced by the injection of 
filtered diphtheritic culture-broths. 

The action of the poison then suffices to deter- 
mine vascular thromboses, which entail either frag- 
mentary destruction of the tissues or a more extensive 
mortification. Then the microbes of putrefaction set 
up a true gangrene. 

The histological lesions of the mucosa subjacent 



to the false membranes have been studied chiefly in 
the throat and air-passages. 

In the diphtheritic amygdalites, the false mem- 
brane is applied to the chorion of the mucosa com- 
pletely denuded of its epithelium. We find on the 
points of the tonsils where the false membrane is 
absent or detached, an epithelium sometimes normal, 
sometimes constituted of one or two layers of cubical 
cells irregularly cylindrical or even vesicular, showing 
a cavity between the protoplasm and the nucleus. 
The chorion is infiltrated with lymph-cells and red 
globules. The capillary vessels are filled with white 
globules; the follicles and reticulated tissue of the 
tonsils are inflamed, stuffed with lymph-cells. When 
there is loss of substance of the mucosa, we find along 
with infiltration of the chorion a softening and sep- 
aration of the connective-tissue fibres by fatty granu- 
lations, as well as the presence of little haemorrhagic 
foci here and there. 

In cutaneous diphtheria, the horny layer has dis- 
appeared, and the derm subjacent to the false mem- 
brane is thickened, red, indurated, and uneven; the 
subcutaneous cellular tissue is infiltrated and tumefied 
so that the borders of the ulceration are very salient 
and violaceous. The rete mucosum and superficial 
layer of the derm react precisely as the epithelium 
and chorion of the mucous membranes, as seen by 
the microscope. 

All the glands are subject to engorgement, espe- 



— 134 — 
daily the submaxillary and parotids. At the autopsy, 
the bronchial and even the mesenteric glands are 
found hypertrophied. The engorged glands may fuse 
together and form a coherent mass, which by its size 
may cause compression symptoms. The cellular 
tissue around the affected glands is infiltrated, and 
the entire region deformed, tense, and hard. 

Section of these glands presents the red or red- 
dish-brown color of intense inflammation. The hyper- 
trophied follicles appear as opaque, white, brilliant 
granules. Centres of necrobiosis have been described. 
Morel refers these lesions to the irritation of strepto- 
cocci in the gland-parenchyma, these microbes being 
always present. The necrobiosis would, then, be the 
result of a secondary infection. He thinks that the 
diphtheria poison causes hypertrophy of the follicles, 
manifesting itself by a considerable accumulation of 
leucocytes which stain vividly. The blood-vessels 
are dilated and contain numerous leucocytes; but the 
stroma, the sinuses, and the capsule of the gland pre- 
sent no alteration. 

In cases where the lesion depends only on the 
action of the diphtheritic poison, no micro-organism 
is seen in the sections. 

The submaxillary and parotid glands present a 
considerable augmentation of volume, have a yellow- 
ish hue, and seem to be the seat of an oedematous 
infiltration. The histological examination shows pro- 
found lesion of their elements. The connective tissue 



— i35 — 
which surrounds the gland and its lobules has pro- 
liferated. The epithelium of the acini is first simply- 
swollen and translucid, then it becomes granular and 
contracts; it may finally so multiply as to obstruct 
the gland cavities by cells of new formation. In 
many points the lobular ducts and acini are surrounded 
by little miliary abscesses. The production of pus in 
these cases must depend on secondary infections. 

Generally voluminous, the liver presents the ex- 
ternal aspect of congestion; it is deep red in patients 
who have succumbed at the onset of diphtheria. In 
cases that have lasted longer it is pale, often mottled 
with yellowish-white patches, indicating fatty accu- 
mulation. On section, no liquid is seen to ooze ex- 
cept in the early stage of congestion, when a little 
dark, thick, sanious fluid escapes. The microscope 
shows dilated capillaries and fatty infiltration of their 
endothelial cells and of the hepatic cells. It is a true 
infiltration and not a degeneration of the hepatic 
cells, for the latter remain living — their protoplasm is 
not modified, their nuclei continue to stain well; at 
the same time, in some cases their volume is notably 
diminished. The fatty accumulation may be peri- 
portal; it may be around the hepatic veins or occupy 
the entire extent of the lobule. Masses of embryonic 
cells may accumulate in the connective tissue of the 
portal spaces, forming nodules. The vessels contain 
a great many leucocytes. In short, the lesions are 
nearly the same as those met with in the liver in the 
course of all infectious diseases. 



— i3 6 — 

Degenerative lesions of the gastric mucous mem- 
brane are common in diphtheria affecting the stomach 
— the epithelium disappearing, subepithelial necrosis 
may follow. The intestine often shows traces of 
catarrhal enteritis, with tumefaction of its follicles 
and glands. 

The spleen is congested and hypertrophied, the 
Malpighian corpuscles white and brilliant; the micro- 
scope shows an enormous accumulation of round cells 
around these corpuscles. 

The lesions of the kidney are those of congestion 
or of parenchymatous nephritis, in general little pro- 
nounced. These lesions are often not symmetrical. 
When there is simply congestion, the kidney is aug- 
mented in volume, of reddish color, its external sur- 
face strewn with deep-red points (Verheyen's stars). 
On section, the congestion is found to be limited to 
the cortical substance, while the medullary substance 
remains pale. — When there is nephritis, the kidney 
is yellow, soft, mottled with spots of a clearer yellow; 
the cortical substance seems augmented in volume, 
is pale on section, and trenches by its prolongations 
on the medullary substance, which is very red; the 
capsule of the kidney is healthy, easily detachable 
without tearing the parenchyma. Under the micro- 
scope the principal lesions, when but little advanced, 
are seen to be dilatation of the blood-vessels and 
some cloudy swelling of the epithelium of the con- 
voluted and collecting tubes — these alterations are 



— i37 — 
similar to those produced by phosphorus or arsenic, 
especially the latter; the glomerule is simply con- 
gested, its vessels distended and full of globules; 
there is rarely any exudation between the capsule 
and capillary tufts. In a more advanced stage, the 
epithelium of Bowman's capsules is in places degen- 
erated and desquamated, in other places undergo- 
ing proliferation; there is a serous exudation, with 
blood-globules and epithelial debris in the cavity of 
the capsule; in the straight and collecting tubes the 
epithelium contains numerous fine fat globules; 
there are little hemorrhagic foci under the capsule, 
and a granular detritus in the large convoluted tubes. 

All these alterations seem due to the intoxica- 
tion, and not to any secondary infection, for all who 
have sought for microbes in a diphtheritic kidney 
have failed to find any. 

The heart is generally increased in size. If in 
many cases pathologists have noted the flabby con- 
sistence and dead-leaf color of the organ when spread 
out on the post-mortem table, it is not rare to observe 
under the microscope the lesions of acute myocarditis 
in a diphtheritic patient whose cardiac tissue remains 
firm, red, and of normal aspect. The heart is dilated, 
but not hypertrophied. Its weight is little if at all 
increased. Generally its cavities and large vessels 
are full of clots, which are either soft, like currant 
jelly (especially in the right cavities), or half fibrinous, 
half cruoric, prolonged into the blood-vessels. When 



- 138 - 
the heart cavities are emptied of their clots, you will 
often see under the endocardium ecchymotic spots, 
and the same may be observed, though rarely, upon 
the pericardium. There is a general or limited red- 
ness at the free border of the valves, and mam- 
millated prominences forming a crown on the upper 
aspect of the valves, principally of the mitral. The 
red coloration of the endocardium is a phenomenon 
of cadaveric imbibition. The mammillated projec- 
tions are the product of fibrous transformation of 
little haematomata developed on the valves during 
early life, and perhaps even during intra-uterine life. 
The histological lesions affect all the elements of the 
structure of the cardiac muscle; they are met with in 
the walls of the left ventricle near the apex, and near 
the columns of the mitral valve. When you dissociate 
the muscular fibres, you observe that they are very fra- 
gile; they are fusiform, tumefied, in many points granu- 
lar, have large nuclei which stain easily and possess one 
or more very refractive nucleoli. The muscular fibres 
may undergo two kinds of degeneration, and present 
either the granular or granulo-fatty aspect or the 
vitreous transformation. In the granular degenera- 
tion the granulations are irregularly disseminated, or 
disposed side by side in chaplets along the fibre. In 
the vitreous degeneration the fibres present one, 
rarely two or three, degenerated patches in their 
course. The vitreous block is spherical or fusiform, 
and crowds to one side the striated substance, swell- 



— i39 — 

ingthe fibre and forming a node in its course. These 
two modes of degeneration may be met in the same 
specimen; the fibre interrupted by waxy blocks pre- 
sents here and there throughout its whole extent a 
crop of dark granulations. The connective tissue 
takes on an abnormal development. The internal 
perimysium is infiltrated with embryonic cells, in the 
midst of which appear debris of granular muscular 
fibres, degenerated, or masses of fatty granulations, 
the' last vestiges of atrophied muscular fibres, or, per- 
haps, little haemorrhagic foci which testify to vascular 
intra-muscular ruptures. In short, the diphtheria 
poison determines both a parenchymatous and an in- 
terstitial lesion. It also causes an arterio-sclerosis of 
the vessels of the heart. The vasa-vasorum situated 
in the outer coats are the seat of an obliterating 
endovascularitis. The walls of the arterioles thicken, 
and their lumen is often filled by a thrombus adher- 
ent to their walls. 

The blood presents modifications of color and 
consistence, which are especially seen in the malignant 
and asphyxiating forms of diphtheria. It is then 
blackish or brown, and has a sepia tint; more rarely 
it has the appearance of currant jelly or simply red- 
dish water. It is probable that the fibrin of the blood 
increases as in most general infectious diseases. The 
researches of Quinquaud, L^corche" and Talamon and 
Binaut, have shown that in diphtheria there is an 
augmentation of the white globules, the more marked 



— 140 — 

the graver the diphtheria. The number of red glob- 
ules diminishes, and, according to Quinquaud, the 
power of absorption of hasmoglobulin for oxygen 
diminishes as the disease becomes more grave. There 
is also a great augmentation of the extractive matters 
of the blood, while the salts of potassa are notably 
diminished. 

The symptoms which seem to depend on the 
alteration of the nervous system are not always ex- 
plained by the lesions found at the autopsy, Very 
complete and extensive paralyses have been noted in 
subjects whose nervous systems presented insignifi- 
cant alterations or none at all. We may, then, affirm, 
in reference to such cases, that the diphtheria poison 
may profoundly modify the function before altering 
the organ. The lesions of the peripheral nerves 
and nerve-roots have been noted in many isolated 
cases since Charcot and Vulpian, in 1862, noticed in 
a case of diphtheritic paralysis of the velum pendulum 
a lesion of the palatine nerves characterized by the 
reduction to granulo-fatty droplets of a certain num- 
ber of nerve-tubes, a lesion similar to what is observed 
at the peripheral end of a divided nerve. Dejerine has 
studied several cases of diphtheritic paralysis, and has 
always noticed in the anterior spinal roots a lesion 
which corresponded exactly by its seat with the para- 
lytic phenomena observed during life, and which was 
the more marked the longer the paralysis had lasted. 
This lesion was identical with the Wallerian degener- 



— i4i — 

ation, characterized by the moniliform aspect of the 
nerve-tubes, in which the myeline breaks up into fat 
drops by the complete disappearance of the axis- 
cylinder and a multiplication of the nuclei of the 
sheath of Schwann. The posterior roots were normal. 
The examination of the peripheral nerve was made in 
only one of these cases. Dejerine noticed these empty 
nerve-sheaths, in the midst of other tubes that were 
perfectly normal. He describes, at the same time, 
slightly marked lesions of the spinal cord, limited to 
the gray substance, but more particularly to the ante- 
rior cornua (nerve-cells less numerous, less refractive; 
multiplication of the elements of the neuroglia; con- 
gestion of the vessels). 

Gombault, whose researches have been con- 
firmed by the observations of Gaucher and Meyer, 
has established the nature of the lesions of the roots 
and peripheral nerves in diphtheritic paralysis. It is 
a periaxile segmentary neuritis, of which the Wallerian 
degeneration is the possible if not necessary termina- 
tion. There is first a segmentary alteration affecting 
only a limited extent of the length of the fibre, 
located in one or more annular segments, often in a 
part of the segment only. When you follow the 
same fibre along its entire course you will not fail to 
meet the same lesion several times, each diseased seg- 
ment being separated from those nearest by intervals 
of fibre absolutely healthy. The diseased fibres have 
a tendency to group themselves into bundles; at the 



— 142 — 

same time, diseased fibres may be met with in the 
midst of healthy fibres. The segmentary lesions 
begin at one of the extremities of the segment; they 
then gain the other, and finally the middle portion. 
The lesion takes on two different aspects: there is a 
phase of degeneration, and a stage of regeneration. 
These two aspects are frequently associated in the 
same interannular segment. In the stage of degen- 
eration the myeline becomes granular; in certain 
points of the nerve tubes there are large protoplasmic 
masses containing numerous nuclei; elsewhere the 
axis-cylinder, under the form of a simple tractus, 
is covered at the level of the granular swellings 
with myeline, but remains always continuous. When 
the fibre is regenerated it is thinner at the point 
where it has been diseased— and the segments that 
have been affected are shorter than normally— but its 
sheath of myeline is perfectly homogeneous and is 
depressed at the level of the nuclei; its contours are 
sharply arrested. The degeneration of the fibre does 
not always retrocede, and the axis-cylinder may be- 
come interrupted by a sort of spontaneous destruction 
similar to what we see in acute myelitis. You will 
note then, in a segment of neuritis, moniliform swell- 
ings of the axis-cylinder, which finally fill the primitive 
sheath; in following the nerve you arrive at a solution 
of continuity beyond which you no longer find it 
except under the form of isolated trunks between the 
blocks of myeline. From this point, where there is 



— 143 — 
rupture of the axis-cylinder, the entire peripheral end 
of the nerve fibre undergoes a Wallerian degenera- 
tion. Thus you will note these lesions alongside of 
those of segmentary peri-axile neuritis, of which they 
are the consequences. Pitres and Vaillard, in exam- 
ining the nerves in a case of diphtheritic paralysis, 
have found the lesions described by Gombault. But 
in the fibres affected with segmentary neuritis they 
have not been able to stain the axis-cylinders. 
Lastly, Babinsky has not succeeded in finding the 
histological lesions of the nerves in experimental 
diphtheritic paralysis. 

The spinal cord has generally presented an 
aspect nearly normal; in some cases the large motor 
cells of the anterior cornua were filled with dark, 
voluminous granulations which completely concealed 
their nuclei and resembled those met with in the 
course of myelitis. 

The meninges present exceptionally the appear- 
ances of inflammation with fibrinous exudation. This 
meningitis may invade the gray substance of the cord 
and constitute a meningo-myelitis, involve the whole 
extent of the bulbo-spinal meninges, or localize itself 
in the bulb and cervical cord. 

In the cerebrum, lesions have been very rarely 
found; those which have been noted were sanguineous 
extravasations with peripheral softening, simple cere- 
bral congestion, turgesence of the sinuses, serous suf- 
fusion of the meninges, oedema of the ventricles, etc. 



— 144 — 
Inflammation of the meninges is quite exceptional 
and is always due to secondary infections. 

The muscles may be altered in diphtheria; writers 
have noted granular degeneration of their fibres. 
The fibrillary elements of the primitive fasciculi lose 
their cohesion and easily separate; their transverse 
striation is effaced; the fibres contain proteinaceous 
or fatty granulations, but there is no alteration of 
neuclei or sarcolemma. Labadie-Lagrave has re- 
ported a case in which the muscles presented the 
waxy transformation. These alterations have been 
especially studied in the muscles subjacent to the in- 
flamed mucous membranes, larynx, and soft palate. 
They are pale, of a dead-leaf color, cedematous, and 
friable. In the larynx the extrinsic muscles are rarely 
degenerated; it is the thyro-arytenoidei which are 
most generally affected. 

3. Lesions Due to Secondary Affections. — 
Ulceration and gangrene of the mucous membranes are 
exceptional in diphtheria. We have seen, however, that 
the diphtheritic poison may of itself in certain cases 
determine losses of substance in mucosae covered with 
false membrane. The streptococcus pyogenes, so often 
associated with the Loeffler bacillus, may also pene- 
trate the mucous membranes and determine profound 
ulcerations: the case is similar to that observed in the 
pseudo-diphtheritic anginas of scarlatina where we 
find extensive losses of substance underneath the false 
membrane, and can easily stain by Gram's method 



— 145 — 
the micrococci in chains which profoundly penetrate 
the diseased mucosa. When the subject is very much 
debilitated, and the microbes of putrefaction obtain a 
habitat in these ulcerations, the base becomes toment- 
ous and grayish, the borders are excavated, and there 
is gangrene at the level of the losses of substance. 
This is met with on the tonsils and soft palate, where 
it may cause perforation. The gangrene may pene- 
trate the cellular tissue below the mucosa and extend 
to the large vessels of the neck. Necrosis of the 
larynx and its cartilages is rare. The gangrene may 
be complicated with cutaneous diphtheria and invade 
the tracheotomy wound after this operation. 

The histological lesions of the glands have been 
well studied by CErtel and Morel. These alterations 
pertain especially to the follicles, which stain poorly 
by picro-carmine. Little alveolar abscesses form in 
the necrosed connective-tissue stroma. In points 
where the lesion is less advanced, we see in the region 
of the follicles a finely granular amorphous tissue in 
which may still be seen a few round-cell elements, 
which stain indifferently by carmine and present the 
characters of coagulation necrosis. Masses of strep- 
tococci are found in the little alveolar abscesses and 
degenerated follicles. 

The inflammations of the endocardium or men- 
inges are complications quite exceptional in diph- 
theria. 

The cutaneous modifications corresponding to 



— 146 — 

erythemata have been studied by Lewin and Leloir. 
They present nothing that is special to diphtheritic 
erythemata. We know that each arteriole of the 
skin irrigates a little circular territory, the arteriole 
dividing and spreading itself out into ramifications in 
the form of a cone, of which the base is tegumentary. 
If an arteriole is paralyzed, all the corresponding 
territory is congested and forms a red spot. At the 
onset of an erythema, the congestion usually shows 
itself in an unequal degree in these different vascular 
territories, so that paler areas are observed between 
the red spots before the erythema becomes general. 
When the blood-pressure equalizes itself over all the 
vascular territories, the coloration of the skin becomes 
the same everywhere and we have the scarlatinoid 
erythema; and if there is exudation under the epider- 
mis, there will be found vesicles or bullae. When the 
congestion remains limited to little islets, but is still 
active and there is oedema and diapedesis from the 
hyperaemic zones, the eruption takes on the papulo- 
tuberculous aspect. If the blood-pressure becomes 
too strong in the territories invaded by the erythema, 
the red blood-corpuscles issue from the vessels, and 
we have the purpuric erythema. 

The most frequent pulmonary lesion of diphtheria 
is broncho-pneumonia. It is the consequence of a 
secondary infection, due to the streptococcus pyogenes. 
This micro-organism is the agent of most of the 
broncho-pneumonias, whether primary or secondary. 



— 147 — 
In six cases out of seven the broncho-pneumonia of 
diphtheria takes on the form of disseminated nodules; 
the pseudo-lobar form which is met with in one out 
of seven cases occupies chiefly the posterior bronchial 
system, generally towards the inferior border. 

Atelectasis is constant and always very ex- 
tensive. It may be the only pulmonary lesion. In 
no disease but whooping-cough is the vesicular 
emphysema more marked; rarely it becomes inter- 
lobular and subpleural. The abundance of the fibrin- 
ous exudate in the alveoli is a character of the 
broncho-pneumonia of the diphtheritic. In certain 
cases the fibrin, under the form of ramified and an- 
astomosing tracts, almost fills of itself a whole group 
of alveoli. This network contains a few leucocytes, 
red globules, and epithelial cells. Its. aspect might 
lead one to believe that he had before him a frank 
pneumonia at the period of hepatization, if these 
points were not immediately surrounded by zones 
showing wide disparities in the state of development 
of the characteristic lesion. These abundant de- 
posits of fibrin are met with in cases where the false 
membranes have extended to the small bronchi, but 
they are also found in cases where the membranes are 
arrested at the larynx or trachea; there is, then, no 
necessary relation between the two processes. 

Another elementary lesion whose frequency is 
rather peculiar to diphtheria, is constituted by hemor- 
rhagic foci in the midst of the pulmonary parenchyma. 



— 148 — 

Balzer has made a study of them, and assigns as their 
habitual seat the posterior and inferior part of the 
lungs. , The blood effused circumscribes the peri- 
bronchial nodules, and deforms but never entirely 
penetrates them. It is probable that we have to do 
here with haemorrhages due to the peri-nodular con- 
gestion and penetrating the lobules primarily affected 
with the pneumonia. Microscopic preparations made 
from sections of the bronchial nodules show the 
streptococcus, and sometimes the pneumococcus and 
Lceffler bacillus. 

I cannot close this chapter without saying a few 
words concerning the lesions produced in the organ- 
ism of animals by experimental diphtheria. 

The researches of Babes have shown that the 
lesions obtained by inoculating the Loeffler bacillus 
in animals are very like those met with in the organs 
of children that have died of diphtheria. The simi- 
larity becomes much less evident when the inocula- 
tion is performed with diphtheritic cultures that have 
been filtered through porcelain. New researches will 
be necessary to explain these differences. 



TREATMENT. 

It is not my intention to review here the innu- 
merable kinds of treatment which have been proposed 
for diphtheria. Their very multiplicity sufficiently 
indicates the little efficacy they possess. I shall only 
attempt to set forth what appear to be the most ra- 
tional precautions and therapeutic measures for the 
physician to adopt when he finds himself in the pres- 
ence of a case of diphtheria. I shall start from the 
postulate, absolutely demonstrated to-day, that the 
germ of diphtheria is exclusively contained in the 
false membranes and products of expectoration, which 
when dried keep the germ active a long time and 
may thus easily transmit it in a state of virulency. 

When the physician is called to a patient affected 
with diphtheria, what should he do ? 

Even when there is some doubt as to the diph- 
theritic nature of the affection, the same precautions 
should be taken as if the diagnosis were certain. 
The carriage which the patient occupies in transit to 
the hospital must be disinfected immediately after. 
In Paris we have special carriages placed at the dis- 
posal of physicians for such purposes. If the patient 
is not to be removed anywhere, he must as far as pos- 
sible be isolated, no one but his regular attendants 
being allowed access to him. If children live in 
the house, they should not only be excluded from 
the room, but if possible sent away during the time 



— iffo — 

of sickness and till after thorough disinfection of the 
house has been effected. These same children should 
also be kept under observation and away from other 
children during the first fortnight. Nurses and at- 
tendants on the patients should rigorously observe 
the following rules: Take no drink or nourishment in 
the sick-room; keep the hands clean with a brush and 
soap-suds, and occasionally rinse them in an anti- 
septic solution; bathe after every contact with an 
infected object; renew these ablutions always on 
leaving the sick-room and before eating. It would 
be a good plan for every attendant to wear a special 
suit while in the patient's room; this can be laid aside 
when he leaves the room. All cracks or abrasions 
about the hands or face must be instantly painted 
with collodion. The nurse should avoid taking the 
patient's breath, especially during fits of coughing. 
Nor should the nurse neglect to take a walk in the 
open air once or twice a day, or overlook the neces- 
sity of sleeping in a room apart from the patient. 
Similar precautions are equally necessary for the 
attending physician. 

There are two sorts of antiseptic solutions to be 
used: one strong, the other weak. The former con- 
sists of corrosive sublimate, one part to a thousand; 
this should be stained with fuchsin, and acidified with 
ten parts of hydrochloric acid: 

Corrosive sublimate, i part. 
Hydrochloric acid, 10 parts. 
Water, iooo parts.',' 



Useful-antiseptic solutions are also the following: 
cup. sulph., 5-per-cent.; calcium chloride, 5-per-cent; 
milk of lime, 20-per-cent.; zinc chloride, i-per-cent. 
To obtain a very active milk of lime, take a certain 
quantity of quick-lime of good quality, and slack it 
by wetting it slowly with half its weight of water; 
when the slacking is completed, put the powder in a 
bottle, cork tightly and set away in a dry place. As 
a kilogramme which has absorbed 500 grammes of 
water in order to undergo slacking has acquired a 
volume of 2 liters 200 cubic centimeters, it suffices 
to suspend it in double its volume of water {i.e., 4 
liters, 400 Cc.) in order to have a milk of lime which 
shall be about 20 per 100. 

The feeble solutions which are most efficacious 
are the following: corrosive sublimate, 1 per 2000; 
phenic acid, 5 per 1000; sulphate of copper, 2 per 
100; chloride of lime, 2 per 100; milk of lime, 7 per 
100. The first two of these feeble solutions are best 
for the ablutions of the patient or his attendants. 

As soon as a case of diphtheria is recognized, all 
•curtains, carpets, wearing apparel, and every article 
of furniture which is not indispensable should be re- 
moved from the sick-chamber, and immediately dis- 
infected, either in the dry stove under steam pressure, 
or by washings with a suitable solution from among 
those above mentioned, or by sulphur fumigations. 
The bed should be located in the middle of the room. 
Aeration of the room must be effected several times a 



— i5 2 — 
day; sawdust wet with one of the strong disinfectant 
solutions should be sprinkled over the floor every day, 
the room then swept, and the sweepings immediately 
burned. The body-linen, towels, bed-clothing, dress- 
ings, etc., ought to be immersed for two hours in one 
of the strong solutions, and then kept in boiling water 
for half an hour, before the final washing. All objects 
that have been in contact with the patient may trans- 
mit the disease; care must therefore be taken that all 
surgical instruments, as well as domestic utensils, 
knives, forks, spoons, cups, etc., after being used, be 
placed in boiling water, and kept there for five minutes 
at least. It will be well to destroy all books and 
playthings which have been handled by the patient. 

The matters vomited or expectorated by the 
patient, the stools, and the urine, should be immedi- 
ately disinfected with one of the strong solutions. A 
cupful of the solution having been poured into the 
vessel, the vomitus, expectoration or dejecta should, 
immediately after passage, be buried or poured into 
water-closets which are disinfected twice a day with 
a strong solution of milk of lime. The better way 
would be to bury them in a deep hole in the ground, 
first covering with the strong chloride of zinc or 
other disinfectant solution. A place should be chosen 
which is at a distance from any water-source. The 
dejecta must not be thrown onto manure heaps or 
into water-courses. 

It is important in the presence of a case of 



— i53 — 
diphtheria that the physician should make a careful 
inquiry to determine its origin; he will thus often be 
able to circumscribe and arrest an epidemic. More- 
over, every case of diphtheria should be at once 
reported to the board of health. 

All these precautions should be indicated by the 
physician at the date of his first visit. 

Local Treatment. — The prevalent conception 
of diphtheria, which makes of it a disease quite local 
at the outset, the patient subsequently being consti- 
tutionally poisoned by the products elaborated at the 
point of infection, gives a capital importance to the 
local treatment of the disease. Cauterization of the 
parts invaded by the false membrane is not a new 
method, and we know the use which Bretonneau and 
Trousseau made of hydrochloric acid for this end. 
But the recent conquests of bacteriology have given 
more assurance to the physician, and he has thereby 
learned the crucial point to which his efforts should 
be directed. M. Gaucher was the first to popularize 
a rational treatment of diphtheria. This method is 
to-day everywhere employed in this country, though 
with some modifications. His mode of treatment in- 
cludes three stages: (i) Ablation of the false mem- 
branes; (2) Painting of the diseased parts with a 
strong antiseptic mixture; (3) Irrigations of the 
bucco-pharyngeal cavity with a weak antiseptic solu- 
tion. These three stages of treatment should be 



— i54 — 
regularly repeated every three or four hours, even 
during the night, and oftener still if the false mem- 
branes are rapidly reproduced. 

The ablation of the false membrane is made by 
means of a soft-wool brush invented by Dr. Cr^san- 
tignes. The mouth must be opened with a tongue- 
depressor, and kept open if necessary by means of a 
wedge, and the false membrane removed very gently, 
care being taken not to corrode the mucosa and 
make it bleed. As far as possible the throat should 
be cleared of all the false membranes which cover it, 
then painted by means of a suitable swab with the 
following mixture: 

Camphor, 20 Gm. 

Castor oil, 15 Gm. 

Alcohol, 10 Gm. 

Crystallized phenic acid, 5 Gm. 

Tartaric acid, 1 Gm. 

This mixture is sufficiently caustic to require care 
on the part of the physician not to touch with it the 
tongue or the sound parts of the mucous membrane 
of the mouth. 

As fast as the false membranes are detached, and 
while there remain any floating shreds in the throat, 
it is well to make from time to time large irrigations 
of the bucco-pharyngeal cavity and nasal fossae with 
a feeble antiseptic solution (phenic acid, 1 per 200), 
These irrigations are made by means of an ordinary 
fountain-syringe with straight cannula, care being 



— i55 — 
taken to have the headf of the child bent over a pail 
or other vessel to prevent swallowing the solution. 
After each cauterization with the mixture, a period of 
ten minutes is allowed to elapse, to give the topical 
remedy time to act, then a copious irrigation is made 
with a weak solution; in very young children it is 
better to employ boiled water. 

Instead of the Gaucher mixture, the sulphoricin- 
ated phenol may be employed with equally good re- 
sults; the bichloride or biniodide of mercury, i part 
to 200 or 300; or the camphorated phenol. 

Crystallized phenic acid, 5 Gm. 
Camphor, 20 Gm. 
Alcohol, 10 Gm. 
Gycerin, 25 Gm. 

The camphorated naphthol is a good preparation: 

Naphthol, 10 Gm. 
Camphor, 20 Gm. 
Glycerin, 30 Gm. 

Salicylic acid may also be used in weak solution, 
1 or 2 per 100. 

Perchloride of iron, pure, or mixed with equal 
parts of glycerin, is also in use; also tincture of iodine; 
lastly, permanganate of potash, 1:10, with which I 
have obtained in a series of clinical trials results very 
similar to those which others claim to have derived 
from Gaucher's mixture. M. D'Espine prescribes 
lemon-juice, which is a very old remedy in diphtheria. 

Good authorities employ also for irrigations 



- 156 - 
boric-acid solutions, 3 or 4 per 100; lime-water; 
chloral-water, 1 per 200; salicylic acid, t per 1000; 
and peroxide of hydrogen. 

Some conjoin with the above, antiseptic sprays. 
With a suitable hand-ball spray-producer, spray the 
mouth and throat of the patient with the antiseptic 
solution. Or steam pulverizations with a boric solu- 
tion may be made, a Codman & Shurtleff atomizer 
being employed; the steam is directed as far as possi- 
ble into the mouth of the patient. The atmosphere 
of the room may also be saturated with antiseptic 
vapor by keeping constantly evaporating a weak 
carbolic solution contained in a great open dish. 
Sevestre advises to place every ten minutes a little 
piece of ice in the mouth of the patient. 

The method of Gaucher, which gives in general 
very satisfactory results, is not applicable to all cases. 
The degree of adhesion of the false membrane is very 
variable. There are diphtherias where the exudate 
seems to be identical with the mucous membrane, and 
where all attempt at ablation ends in tearing the 
mucosa and making it bleed. Often the pseudo- 
membrane which is easily removable at the onset of 
the disease, becomes subsequently extraordinarily ad- 
herent to the underlying mucosa. Sometimes we en- 
counter infants so refractory that at each swabbing 
we run the risk of making a traumatism more or less 
deep in the mouth or in the throat with the tongue- 
depressor or with the swab forceps, especially when 



— i57 — 
the attendant does not well succeed in keeping the 
child still. It seems to me that these are real contra- 
indications against swabbing. Such is, moreover, the 
opinion of M. Roux, who said recently: " I am not at 
all an advocate of forcible swabbing and ablation 
of the pharyngeal false-membranes. By these meth- 
ods one cannot help continually wounding the sur- 
face of the tonsils. In destroying the false mem- 
branes you destroy also certain parts of the mucosa, 
and you create new points of absorption for the 
toxine which is being continually produced by the 
microbes which pullulate in the epithelium. It will 
not do to believe, in fact, that even when you have 
removed all the white patches in the throat you have 
removed all the cause of the evil; it is far otherwise. 
There remains always a residuum of bacilli that the 
most energetic brushings cannot remove. In my 
judgment it is better practice to content ourselves 
with antiseptic irrigations, abundant and repeated, 
made with care and gentleness." The practitioner will, 
then, limit himself to irrigations of the throat with 
one of the solutions which I have indicated above, 
whenever he has reason to fear that, by attempting to 
swab, he will wound the mucosa. 

The local treatment which I have described is 
chiefly applicable to diphtheritic angina; but it is 
also employed, whatever may be the seat of the false 
membranes, whenever they are directly accessible. 

When the diphtheria is developed on a cutanepus 



- i58- 
surface, it is necessary besides to cover the wound 
with an occlusive dressing which will prevent the dis- 
semination of the disease. 

Whenever the false membrane invades the larynx 
it constitutes a mechanical obstacle to respiration 
which may necessitate tracheotomy. I shall not here 
describe this operation or its sequelae; but it is well to 
remember that, except in certain cases where the very 
intense and oft-repeated paroxysms of suffocation 
threaten sudden death, it is the rule not to operate 
until the period of asphyxia, when to the extinction 
of the voice and the cough is added a dyspnoea not 
only paroxysmal but permanent, with wheezing and 
signs of blood-stasis in the capillaries. It is better, 
in short, to operate at the latest possible moment, and 
not to forget that often an emetic suitably adminis- 
tered has enabled the physician to avoid an operation 
which before seemed necessary. 

General Treatment. — At the same time that 
we combat the infection we must arm the organism 
against the intoxication by subjecting it to an appro- 
priate general treatment, of which alimentation and 
tonics form the basis. 

It is needful, above all, to nourish the patient 
as fully as possible. It is also necessary to overcome 
the dysphagia, and the repugnance which the patients 
rapidly manifest toward food; to have recourse to 
semi-solid and very substantial articles of diet in 



— i59 — 
small volume, such as eggs, meat-juice mixed with 
thick gruel, creams, scraped or very finely hashed 
meat. The physician will employ, in case of neces- 
sity, gavage (forced feeding) and even nutritive 
enemata. Alcoholic stimulants give also good results, 
on condition that they are diluted with water and 
given in small quantities at a time. According to 
the taste of the patient, he may be allowed to take 
freely sherry, Malaga, champagne or Bordeaux wine, 
whiskey punch, tea and coffee. All these liquids are 
better tolerated and more easily swallowed when they 
are cold, and even ice-cold. 

I am in the habit of giving cinchona, under the 
form of the soft extract, in the dose of two to four 
grammes per day, in infusion of coffee: 

3 Inf. coffee, 125 Gm. 

Syr. acaciae, 40 Gm. 

Soft ext. cinchona, 2 to 4 Gm. 
M. S.: Tablespoonful every two hours. 

Some think highly of hydrochloric lemonade, 
4 per 1000— taken continually by spoonfuls during 
the day; perchloride of iron, in the dose of one to 
two drops (liq. ferri chloridi) every two hours; euca- 
lyptol, dissolved in liquid vaselin, in subcutaneous 
injection ; two to five grammes of benzoate of soda per 
day in a potion; hypodermic injections of caffeine or 
of ether; lastly, inhalations of oxygen. 



— 160 — 

Treatment of Certain Signs of Intoxica- 
tion. — When the glandular engorgement takes on 
considerable proportions, the practitioner may make 
inunctions of mercurial ointment over the swollen 
parts, or he may keep on cold applications, and even 
apply an ice-bag. 

In general, the albuminuria is too transitory to 
indicate a lasting lesion of the kidney. If, however, 
it is persistent and remains abundant, it will be desir- 
able to put the patient on a milk diet, while continu- 
ing to stimulate him with a little brandy. 

In cases where the gastro-intestinal symptoms 
assume a certain importance, it may be well to prac- 
tice intestinal antisepsis by betol or benzo-naphthol. 

Haemorrhages are rarely so abundant as to re- 
quire treatment; they imply a profound alteration 
of the economy which calls for tonics and stimulants. 

When the heart is gravely affected by the diph- 
theritic poison, and even when it begins simply to be 
enfeebled, it will not do to hesitate to resort to the 
cardiac tonics. Caffeine gives the best results, ad- 
ministered in potion or in hypodermic injection. In 
the adult one to two grammes of caffeine may be 
given per day; in the infant, 25 to 50 centigrammes. 
Black coffee may be taken at the same time. When 
myocarditis is made manifest by incontestable signs, 
give ergotin in the dose of two to four grammes in 
twenty-four hours. Cutaneous revulsion over the 
precordial region seems to present more disadvan- 



— 161 — 

tages than benefits. Diuretics and the milk diet are 
indicated in order to cause the elimination of as 
much as possible of the poison by the renal emunc- 
tory. 

For the diphtheritic paralysis the physician can 
do little but feed the patient and electricize the en- 
feebled muscles. Alimentation should be very care- 
fully watched. It is necessary to diminish as much 
as possible the quantity of liquid aliments when the 
soft palate is affected by the paralysis. Fluids are 
then rejected by the nares, or flow into the respir- 
atory passages, provoking violent paroxysms of 
coughing, which fatigue the patient and cause repug- 
nance toward food. Likewise solid food constitutes 
a danger always threatening; fragments insufficiently 
masticated may fall into the trachea and determine 
an access of fatal suffocation. It is better to give 
panada, thick soups, stews, pap. It may become 
necessary to employ the oesophageal sound to intro- 
duce aliments. At the same time, it is necessary to 
have recourse every day to faradization of the para- 
lyzed muscles. Some have counseled the galvanic 
current, for which success has been claimed; the 
negative pole is placed on the back of the neck, the 
positive pole over the paralyzed parts. 

When the paralysis begins to amend, we may 
attempt to excite the muscular contractility by giving 
preparations of nux vomica. It must be remembered, 
however, that at the onset of the paralysis this is in- 



— 162 

jurious rather than useful. The various tonics, hydro- 
therapy, sulphur baths and sea baths are still precious 
adjuvants. 

Treatment of the Secondary Infections. — 
When below the false membranes there appear patches 
of sphacelus of considerable extent, it will not do to 
neglect repeated antiseptic irrigations, and particularly 
the employment of dioxide of hydrogen; the attempt 
must especially be made to modify the soil by build- 
ing up the organism through super-alimentation and 
tonics. 

The suppurative adenites should be incised early, 
especially if the pus has invaded the cellular tissue 
adjoining the inflamed glands. The least delay at 
this time may permit burrowing of the pus into the 
deep regions of the neck, or even to the mediastinum. 
It must also be remembered that often these abscesses 
comprise two pockets, united by a narrow tract; the 
abscesses should be opened by a free incision, includ- 
ing both cavities. 

It is necessary to cover with occlusive and anti- 
septic dressings all suppurative lesions of the skin or 
cellular tissue (impetigo, whitlows, etc.) which are sus- 
ceptible of being infected by the diphtheritic bacillus. 

Treatment may be efficacious in the tardy bron- 
cho-pneumonias; it is rarely so in the early forms.. 
At the onset, emetics have been recommended; these, 
however, should not be continued, on account of the 



- i6 3 - 

gastric troubles which they entail. The physician 
should have recourse to generous diet (milk, broth, in 
small quantities), tonics, and alcohol. Legroux employs 
systematically as internal treatment, glycerinized 
creosote in rum, to combat and even to prevent the 
broncho-pneumonia. Potions may be given contain- 
ing an expectorant (kermes, or the white oxide of an- 
timony) or tincture of digitalis. Dry cups constitute 
an excellent means of revulsion, preferable to the 
fly-blister. The latter should be absolutely proscribed 
in young children, mustard sinapisms being used 
instead. Following tracheotomy, certain prophylactic 
measures against broncho-pneumonia are absolutely 
indispensable: a muslin band passed across the 
orifice of the cannula, a constant temperature from 
i6° to i8° C. (57 to 6i° F.), and saturation of the 
atmosphere of the room with the vapor of carbolic 
acid from a plate containing this liquid in a state of 
evaporation. 

Hygiene of Convalescence. — We know that 
frequently, when the false membrane has disap- 
peared, the diphtheria bacillus still maintains a 
habitat in the mouth of the patient, and with all its 
virulence. It is necessary, then, long to continue the 
antiseptic lavages of the buccal cavity. It is also 
well to keep the convalescent away from other 
children for a month or more. Before allowing him 
to associate with other children again, it will be pru- 



— 164 — 

dent to make him take one or more sublimate baths, 
or, if that be not possible, a bath of soap and water, 
followed by lotions of corrosive sublimate 1: 1000. At 
the end of convalescence, to complete the toning up 
of the constitution, the patient may be sent away for 
change of air, to the country or sea-side. 

All the objects which have served for the daily 
use of the patients must be disinfected at this time if 
they have not been before. This disinfection is 
effected by prolonged boiling, or by exposure to steam 
under pressure. 

The room that the patient has occupied must not 
be again used until after complete disinfection by one 
of the following processes: 

1. Disinfection by Corrosive Sublimate. Disinfec- 
tion of the bare walls and ceilings should be made 
methodically by means of sprayings with the strong 
solutions of corrosive sublimate. The sprayings 
should be begun at the upper part of the walls, being 
made along a horizontal line and successively carried 
downwards, so that the entire surface of the walls 
shall be covered with a fine stratum of the pulverized 
liquid. The ceiling should be sprayed in the same 
manner. The floors, wainscoting and mantels should 
be washed with boiling water and wiped, then flooded 
with the sublimate solution; and the room should not 
be occupied again until after being thoroughly venti- 
lated for at least twenty-four hours. 

In case the sick-room has been covered with wall- 



- i6 5 - 

papers it will be well to have these scraped off before 
the disinfection, even at the expense of repapering 
the room. 

2. Disinfection by Sulphurous Acid. Paste a few 
strips of paper over all cracks which may allow the 
sulphurous vapors to escape. Remove wall papers 
and scrape the walls. Burn sulphur, thirty to forty 
grammes per cubic meter, in the room. To pre- 
vent the danger of fire, place the vessels containing 
the sulphur in the centre of iron basins containing a 
little water. In order to ignite the sulphur, wet it 
with a little alcohol. Before fumigating the room, it 
is well to saturate the atmosphere with the vapor of 
boiling water, for it has been demonstrated that the 
antiseptic action of sulphurous acid is increased when 
it is mixed with the vapor of water. When the sul- 
phur is ignited, close the doors and windows. The 
room must be kept closed for twenty-four hours; 
then the doors and windows are opened wide, and 
left open for forty-eight hours that the sunlight and 
air may have free access. 

When a region is the seat of an epidemic of 
diphtheria, it is well, whenever this is possible, to re- 
move far from the centre of contagion all persons 
susceptible of contracting the disease, particularly 
children. Careful supervision should be made of the 
drinking-water, which should be of perfect purity, 
and it is better always to use boiled water for cooking 
and for drinking. 



— 166 — 

The washing of contaminated clothing in water- 
courses should be prohibited, and such streams should 
be especially kept free from the dejecta of patients. 

Milk may serve as a vehicle for the diphtheritic 
contagion, and should always in times of danger be 
boiled before being used. 

We have seen that there exist in domestic ani- 
mals certain pseudo-membranous affections which do 
not appear to have the same origin as human diph- 
theria. When these diseases have been observed in a 
stable or barnyard it will be well to isolate the affected 
animals, more for the safety of the animals remaining 
healthy than to arrest an outbreak of human diph- 
theria. 

There are certain general measures of public 
hygiene which should be attended to. All the causes 
which prepare the soil for the invasion of epidemics 
should be removed when diphtheria prevails. It is 
necessary to have a close supervision over groups of 
children such as are assembled in schools, and in times 
of epidemic make frequent examinations of the throat; 
and school children should be required twice a day 
to gargle the mouth with an antiseptic solution. 
Should several cases of diphtheria occur at short 
intervals in a school, there should be no hesitation in 
closing the school. Besides, the rules of general 
hygiene applicable at all times should be still more 
rigorously observed, especially in what concerns the 
purity of the drinking-water; aggregations of indi- 



- i6 7 - 

viduals, as on holidays and at fairs; the superintend- 
ence and provisioning of the markets; the cleanliness 
of the soil; the careful control of water-sources, and 
the investigation of possible causes of infection; the 
regular removal of all night-soil; the cleanliness of 
dwelling-houses; the careful inspection of work-shops, 
dock-yards, etc., destined for the laboring and indus- 
trial population; the purification and regular disin- 
fection of water-closets, public and- private; and the 
maintenance of a perfectly intact and well flushed 
sewerage system. 



INDEX. 



A. 

Page 

Ablation of false membranes * 154 

Albuminuria in diphtheria 75 

Alcoholic stimulants in diphtheria xxi, 159 

Animal diphtheria 58 

Antisepsis in diphtheria viii, 150-156 

Antiseptic solutions for diphtheria 150 

Aviary diphtheria 60 

B. 

Bacillus of Loeffler 23 

Bacteriology of diphtheria 12 

Billington xii 

Blood, the, in diphtheria 139 

Boric-acid solutions , 156 

Bovine diphtheria 61 

Bretonneau , 3, 5, 132 

Broncho-pneumonia in diphtheria 92, 114, 146 

— treatment of 163 

C. 

Cadet de Gassicourt xv 

Caffeine in diphtheritic myocarditis 160 

Camphor, phenicated viii, 154 

Carbolic acid (see Phenic). 

Castor oil and camphor mixture 1 54 

Cauterizations in diphtheria viii, 154 

Cinchona in diphtheria 159 

Contagiousness of diphtheria 14 

Cornil on false membrane 130 



Page 

Corrosive-sublimate treatment • xiv 

Cousot xv 

Croup 63 

in the adult 104 

Culture of Loeffler's bacillus 21 

D. 

Diarrhoea in diphtheria 76 

Diet in diphtheria 158 

Diphtheria, clinical forms of 95 

definition 1 

diagnosis 115 

etiology and bacteriology 11 

history 3 

in adults 104 

in animals 58 

its poison 38 

pathological anatomy 126 

prognosis 112 

progress, duration, etc 108 

secondary infections in 49 

symptoms 64 

treatment of 150 

Disinfection in diphtheria 164 

E. 

Emetics in croup 162 

Enemata. nutritious, in diphtheria 159 

Ergotin in diphtheria 160 

F. 

False diphtherias 56, 120 

Feeding in diphtheria 15S 

G. 

C-aucher 153 



— 171 — 

Pag* 

General treatment 158 

Gentian violet 18 

Glandular engorgement, treatment of 160 

Guelpa xiv 

H. 

Heart in diphtheria 78, 137 

Home 4 

Hydrogen peroxide in diphtheria I5§ 

Hygiene of convalescence 163 

of nurses * 150 

of the sick-room 152 

Hypertoxic diphtheria no 

Iron, perchloride of xiv, xx, 155 

Irrigations in diphtheria xiv, 156 

J- 

Jacobi xii 

K. 

Kidneys in diphtheria 136 

Klebs 3, 8 

L. 

Laryngismus stridulus 118 

Leloir's views of false membranes 129 

Lemonade, hydrochloric 159 

Lemon-juice in diphtheria 155 

Local treatment of diphtheria (see also Preface) 153 

Loeffler 3, 3 

Loeffler's blue 17 

serum 20 

M. 
Milk as a vehicle of contagion 166 



— 172 — 

Page 

Milk-of-lime solution 151 

Muscles, alteration of, in diphtheria 144 

Myocarditis, diphtheritic 80 

N. 

Nerves, lesions of, in diphtheria 140-144 

Neuritis 141 

O. 

Oertel xii 

P. 

Paralysis, diphtheritic 80 

Phenic acid xii, 154 

antiseptic mixture 33 

Peripheral neuritis 141 

Pilocarpine xxi 

Prophylaxis 166 

Pseudo-membranes, histology of 130 

Puerperal diphtheria 123 

Pulse in diphtheria 78 

Q. 

Quinine xxi 

R. 

Resorcin in diphtheria xii 

Roux and Yersin 3, 9, 36, 53, 124 

on forcible swabbing 157 

Roux's blue 18 

S. 

Secondary diphtherias 106 

Smith, J. Lewis xxi 

Sprays, antiseptic, in diphtheria 156 

Steam pulverizations 156 



— 173 ~ 

Page 

Sulphoricinated phenol 33, 155 

Syphilides, pseudo-membranous 125 

T. 

Thrush differentiated from diphtheria 117 

Tracheotomy 93 

Trousseau 4, 5 

U. 
Urine in diphtheria 75 

V. 
Virchow on false membranes 128 

W. 

Wagner's description of false membranes 12S 

Weak antiseptic solutions 151 

Y. 

Yersin (See Roux). 

Z. 
Zannelis. xxii 



BROMELIN. 

A digestive principle from Ananas sativa, Schult. (common Pineapple). 



The discovery by Senor Vincente Marcano, of 
Caracas, Venezuela, that plants of the natural order 
Bromeliaceae contain a proteid-digesting principle simi- 
lar in its effects to pepsin, has excited a great deal of 
interest. 

The common pineapple is the best known repre- 
sentative of the family in question, and the discovery 
therefore constitutes a scientific endorsement of the 
empirical reports that are continually emanating from 
the Southern States of the efficacy of the juice of this 
fruit in the treatment of diphtheria and so-called diph- 
| theritic sore-throat. 

Papain, another well known vegetable ferment, has 
been used in these troubles for a considerable time, but, 
owing to an inherent deficiency, its digestive strength is 
so slight that little success attends its use. 

This preparation of Bromelin, on the other hand, 
is found to possess extraordinary powers in dissolving 
and removing the false membrane of diphtheria and 
other morbid exudates. We therefore invite for it a 
careful trial, confident that the results will justify all 
that has been said in praise of pineapple-juice. 



PARKE, DAYIS & CO., 

DETROIT, NEW YORK, KANSAS CITY, U. S. A. 

LONDON, ENG., «nd WALKERVILLE, ONT. 



BUE)E)ETIN «»* PUBLICATION^ 

-OF - 

GEORGE S. DAVIS, Publislier. 

THE THERAPEUTIC GAZETTE. 

A Monthly Journal of Physiological and. Clinical Therapeutics. 

EDITED BY 

H. A. HARE, M. D., G. E. DeSCHWEINITZ, M. D., EDWARD MARTIN, M. D. 
SUBSCRIPTION PRICE, $2.00 PER YEAR. 

THE INDEX MEDICUS. 

A Monthly Classified Record of the Current Medical Literature of the World. 

COMPILED UNDER THE DIRECTION OF 

DR. JOHN S. BILLINGS, Surgeon U. S. A., 

and DR. ROBERT FLETCHER, M. R. C. S., Eng. 
SUBSCRIPTION PRICE, $ 1 0.OO PER YEAR. 

THE AMERICAN LANCET. 

EDITED BY 

LEAETTIS CONTSrOR, 3Vt. JD. 

A MONTHLY JOURNAL DEVOTED TO REGULAR MEDICINE. 

SUBSCRIPTION PRICE, $2.00 PER YEAR. 

THE MEDICAL AGE. 

A Semi-Monthly Journal of Practical Medicine and Medical News. 
SUBSCRIPTION PRICE, $1.00 PER YEAR. 

THE "WESTERN MEDICAL REPORTER. 

EDITED BY 

0". IE. ZHZ-A-ZRIPIEilR,, -A.. HM., OUT.. 3D. 

A MONTHLY EPITOME OF MEDICAL PROGRESS. 

SUBSCRIPTION PRICE, $1.00 PER YEAR. 

THE BULLETIN OF PHARMACY. 

A' Monthly Exponent of Pharmaceutical Progress and News. 
SUBSCRIPTION PRICE, $ 1 .OO PER YEAR. 



New subscribers taking more than one journal, and accompanying subscription 
by remittance, are entitled to the following special rates: 

Ifcr GAZETTE and AGE. $-2.50 : GAZETTE. AGE and LANCET. $4.00; LANCET 
and AGE, $2.50 ; WESTERN MEDICAL REPORTER or BULLETIN with any of 
the above, except the Index Medicus, at 20 per cent, less than regular rates. 

Combined, these journals furnish a complete working library of current medi- 
cal literature, all the medical news, and full reports of medical progress. 



GEO. S. DAYIS, Publisher, Detroit, Mich. 



IN EXPLANATION OF 



Bb Physician's Leisure Library. 

This series has been universally commended by the medical press and profes- 
sion; it represents a new era in the publication of medical books. 

In the belief that these short practical treatises, prepared by well known 
authors, containing the gist of what they had to say regarding the treatment of 
diseases commonly met with and of which they had made a special study, sold at a 
small price, would be welcomed by the majority of the profession, this form of pub- 
lication was undertaken. 

The books are amply illustrated, and issued in attractive form in durable paper 
covers, and in cloth. 

PHYSICIAN'S LEISURE LIBRARY 

PRICEs PAPER, 25 CTS. PER COPY, $2,50 PER SET; CLOTH, 50 CTS, PER COPY, 
$5.00 PER SET. 



SERIES 

Inhalers, Inhalations and Inhalants. 
By Beverley Robinson, M.D. 

The Use of Electricity in the Removal of 
Superfluous Hair and the Treatment of 
Various Facial Blemishes. 
By Geo. Henry Fox, M.D. 



New Medications. Vol.1. 
New Medications. Vol.11. 

By Dujardin-Beaumetz, M.D. 

The Modern Treatment of Ear Diseases. 
By Samuel Sexton, M.D. 

The Modern Treatment of Eczema. 
By Henry G. Piffard, M.D. 



Antiseptic Midwifery. 

By Henry J. Garrigues, M.D. 
On the Determination of the Necessity for 
Wearing Glasses. 

By D. B. St. John Roosa, M.D. 
The Physiological, Pathological and Ther- 
apeutic Effects of Compressed Air. 

By Andrew H . Smith, M.D. 
GranularLidsandContagiousOphthalmia. 

By W. F. Mittendorf.M.D. 
Practical Bacteriology. (Out of print.) 

By Thomas E. Satterthwaite, M.D . 
Pregnancy, Parturition, the Puerperal 
State, and their Complications. 

By Paul F. Munde\ M.D. 



SERIES II. 



The Diagnosis and Treatment of Haem- 
orrhoids. 

By Chas. B. Kelsey, M.D. 

Diseases of the Heart. Vol. I. 
Diseases of the Heart. Vol. II. 
By Dujardin-Beaumetz, M.D. 

The Modern Treatment of Diarrhoea and 
Dysentery. 

By A. B. Palmer, M.D. 

Intestinal Diseases of Children. Vol. i. 
Intestinal Diseases of Children. Vol. U. 
By A. Jacobi. M.D. 



The Modern Treatment of Headaches. 
By Allan McLane Hamilton, M.D. 

The Modern Treatment of Pleurisy and 
Pneumonia. 

By G. M. Garland, M.D. 

Diseases of the Male Urethra. 
By Fessenden N. Otis, M.D. 

The Disorders of Menstruation. 
By Edward W. Jenks, M.D. 

The Infectious Diseases. Vol.1. 

The Infectious Diseases. Vol. II. 

By Karl Liebermeister. 



SERIES III. 



Abdominal Surgery. 

By Hal C. Wyman, M.D. 
Diseases of the Liver. 

By Dujardin-Beaumetz, M.D. 
Hysteria and Epilepsy. 

By J. Leonard Corning, M.D. 
Diseases of the Kidney. 

By Dujardin-Beaumetz, M.D. 

The Theory and Practice of the Ophthal- 
moscope. 

By J. Herbert Claiborne, Jr., M.D. 
Modern Treatment of B right's Disease. 

By Alfred L. Loomis, M.D. 



Clinical Lectures on Certain Diseases et 
the Nervous System. 

By Prof. J. M. Charcot, M.D. 
The Radical Cure of Hernia. 

By Henry O. Marcy, A.M., M.D., 
LL.D. 
Spinal Irritation. 

By William A. Hammond, M.D. 
Dyspepsia. 

By Frank Woodbury, M.D. 
The Treatment of the Morphia Habit. 

By Erlenmeyer. 
The Etiology, Diagnosis and Therapy of 
Tuberculosis. 

By Prof. H. von Ziemssen. 



SERIES ITT. 



Nervous Syphilis. 

By H. C. Wood, M.D. 
Education and Culture as correlated to 
the Health and Diseases of Women. 

By A. J. C.Skene, M.D. 
Diabetes. 

By A. H. Smith, M.D. 
A Treatise on Fractures. 

By Armand Despres, M.D. 
Some Majorand Minor Fallacies concern- 
ing Syphilis. 

By E. L. Keyes, M.D. 
Hypodermic Medication. 

By Bourneville and Bricon. 



Practical Points in the Management of 
Diseases of Children. 
By I. N. Love, M.D. 
Neuralgia. 

By E. P. Hurd, M.D. 
Rheumatism and Gout. 

By F. Le Roy Satterlee, M.D. 
Electricity, Its Application in Medicine. 
Vol.1. 
Electricity, Its Application in Medicine. 
Vol.11. 
By Wellington Adams, M.D. 
Auscultation and Percussion. 

By Frederick C. Shattuck, M.D. 



SERIES V. 



Taking Cold. 

By F. H. Bosworth, M.D. 

Practical Notes on Urinary Analysis. 
By William B. Canfield, M.D. 

Practical Intestinal Surgery. Vol. I. 
Practical Intestinal Surgery. Vol. II. 
By F. B. Robinson. M.D. 

Lectures on Tumors. 

By John B. Hamilton, M.D., LL.D. 

Pulmonary Consumption, a Nervous Dis- 
ease. 

By Thomas J . Mays, M.D. 



Artificial Anaesthetics and Anaesthesia. 
By DeForest Willard, M. D., and 
Lewis H. Adler, Jr., M. D. 

Lessons in the Diagnosis and Treatment 
of Eye Diseases. 

By Casey A. Wood, M.D. 
The Modern Treatment of Hip Disease. 

By Charles F. Stillman, M.D. 
Diseases of the Bladder and Prostate. 

By Hal C. Wyman, M.D. 
Cancer. 

By Daniel Lewis, M.D. 
Insomnia and Hypnotics. 

By Germain See. 

[Translated by E. P. Hurd, M.D.] 



SERIES VI. 



The Uses of Water in Modem Medicine, i Gonorrhoea and Its Treatmen 

Vo1, 1 ■ By G. Frank Lydston , M . D . 

The Uses of Water in Modern Medicine Acne and Alopecia. 

By Simon Baruch, M.D. By L. Duncan Bulkley. M.D. 

The Electro-Therapeutics of Gynaecol- j Fi«ure of the Anus and Fistula in Ano. 

ogy. Vol. I. (In cloth only.) By Lewis H. Adler, Jr., M.D. 

The Electro-Therapeutics of Gynaecol- ! The Surgical Anatomy and Surgery of 
ogy. Vol.11. (In cloth only.) 



By A. H. Goelet, M.D. 

Cerebral Meningitis. 

By Martin W. Barr, M.D. 



By Albert H. Turtle, M.D., S.B. 

Recent Developments in Massage. 
By Douglas Graham, M.D. 



Contributions of Physicians to English j Sexual Weakness and Impotence, 
and American Literature. (In cloth only.) 

By Robert C. Kenner, M.D. By Edward Martin, M.D. 



SERIES VII. 



Appendicitis and Perityphlitis. 

By Charles Talamon, M.D. 
Cholera. Vol. I. 
Cholera. Vol. n. 

ByG. Archie Stockwell, M.D..F.Z.S. 
Electro-Therapeutics of Neurasthenia. 

By W. F. Robinson, M.D. 
Treatment of Sterility in the'.Woman. 

By Dr. De Sinety. 
Bacterial Poisons. 

By N. Gamalela, M.D. 



The Modern Climatic Treatment of In- 
valids with Pulmonary Consumption in 
Southern California. 

By P. C. Remondino, M.D. 
Antiseptic Therapeutics. Vol. i. 
Antiseptic Therapeutics. Vol. II. 

By E. Trouessart, M.D. 

Treatment of Typhoid Fever. 

By D. D. Stewart, M.D. 

Whooping Cough. Vol.1. 

Whooping Cough. Vol.11. 

By H. Richardiere, M.D. 

[Translated by Joseph Helfman.] 



GEORGE S. DAVIS, Publisher, 

F. O. Box 470 HDetrolt, 2v£icli. 



BOOKS BY LEADING AUTHORS. 



A PRIMER OF PSYCHOLOGY AND MENTAL DISEASE. .$ i.oo 
By Dr. C. B. Burr. 

Part I is devoted to the study of the faculties of the normal miDd, and these 
are plainly and clearly set forth. Part II is devoted to mental diseases, 
causes and forms of insanity being discussed in accordance with an orig- 
inal plan of the author's. Part III deals with the management of cases 
of insanity. 

REACTIONS 2.00 

By F. A. Fllickiger, Ph.D., M.D. 

A Selection of Organic Chemical Preparations Important to Pharmacy in re- 
gard to their Behavior to Commonly Used Reagents. Translated, revised 
and enlarged by J. B. Nagelvoort, analytical chemist to the Pharm.-Chem. 
Laboratory of Parke, Davis & Co. Authorized English edition. 

TABLES FOR DOCTOR AND DRUGGIST 2.00 

Compiled by Eli H. Long, M.D. 

Comprising Tables of Solubilities, Reactions and Incompatibles, Doses and 
Uses of Medicines, Specific Gravity. Poisons and Antidotes, Thermomet- 
ric Equivalents, and The Metric System. SECOND EDITION— En- 
larged and Revised. 

THE PHARMACOLOGY OF THE NEWER MATERIA 
MEDICA— 

Price, postpaid, in cloth 3 . 00 

Price, postpaid, in sheep 3.50 

THE PRINCIPLES AND PRACTICE OF BANDAGING.... 3.0c 
By Gwilym G. Davis, M.D., Universities of Pennsylvania 
and Gottingen. 

The most modern and complete work on bandaging ever issued. Contains 
172 illustrations, prepared from sketches especially made for this book by 
the author, printed from 23 plates on separate pages. The book is hand- 
somely printed on superior quality of paper, with wide margin, and taste- 
fully bound in red cloth. 

SEXUAL IMPOTENCE IN MALE AND FEMALE (3d Edition). 3.00 
By Wm. A. Hammond, M.D. 

Probably more unhappiness is caused by sexual impotence than by any other 
disease that affects mankind. Dr. Hammond discusses Causes, Symp- 
toms and Treatment. 

CLINICAL THERAPEUTICS 4-00 

By Dujardin-Beaumetz, M.D. 
Dujardin-Beaumetz is easily chief in the field of original therapeutic research 
and in fertility of therapeutic suggestion. This treatise of 491 pages 
comprises his lectures on the Treatment of Nervous Diseases, General 
Diseases, and Fevers. 



PHYSICIANS' PERFECT VISITING LIST $ 1.50 

By G. Archie Stockwell, M.D. 

Physicians are generally admitted to be exceedingly poor financiers. There is 
probably no class of professional men who realize so little financially from 
their labors. One cause of this is negligence in keeping an account of their 
work. This call or visiting list has been constructed to enable physicians 
more easily to keep an accurate record of their services. It is arranged 
for perpetual use, and every physician should avail himself of this ready 
and simple method of keeping his accounts on a business basis. 

PALATABLE PRESCRIBING (Third Edition) 1 .00 

By B. W. Palmer, A.M., M.D. 
This book contains over 600 favorite formulas of the most eminent medical 

authorities, culled from their published writings and private records, and 

embraces a resume of the most eligible preparations for the administration 

of the more recent additions to the materia medica. 

A NEW TREATMENT OF CHRONIC METRITIS 50 

By Dr. Georges Apostoli. 
This book of no pages, illustrated with cuts of apparatus, presents the details 

of Apostoli's treatment by intra-uterine Chemical Galvano-Cauterizations 

of Chronic Metritis and Endometritis. 

SANITARY SUGGESTIONS (Paper) 25 

By B. W. Palmer, M.D. 

FORMULA FOR THROAT AND LUNG DISEASES 25 

By E. L. Shurly, M.D. 
These are formulae which Dr. Shurly employs in hospital and private practice, 

and which he has published at the solicitation of his students. 

UNUSUAL BARGAIN! 

The following three books will be sold, for a limited time, at half their 
regular price. Prices quoted are strictly net cash with order. 

UNTOWARD EFFECTS OF DRUGS $ 1.00 

By L. Lewin, M.D. 

MICROSCOPICAL DIAGNOSIS 1.50 

By Chas. H. Stowell, M.S. 

SELECT EXTRA-TROPICAL PLANTS 1.50 

By Baron Ferd. von Mueller. 

GEO. S. DATTIS, Publisher, 

P. O. Box 470, 

DETROIT, - - MICH. 



029 827 958 7 



